CLINICAL CONSULTATION Medication absorption
C L I N I C A L C O N S U LTAT I O N
Medication absorption considerations in patients with postpyloric enteral feeding tubes Chelsey M. McIntyre and Heather M. Monk
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edication administration via the gastrointestinal tract is not straightforward in all patients. There is an occasional need to bypass the stomach with an enteral feeding tube (i.e., postpyloric feeding tube), allowing for administration of both food and medication directly into the small bowel. Acutely ill patients may require a postpyloric feeding tube due to acute gastrointestinal discomfort or vomiting. Chronically ill patients may require the placement of such a tube for a variety of reasons, such as delayed gastric emptying (gastroparesis), chronic nausea or vomiting, and severe reflux.1 Routes of enteral access Many different routes of enteral access may be used for the postpyloric administration of food and medications. Routes of enteral access are described by the anatomical site of insertion and the site of termination. Nasogastric tubes and gastrostomy tubes deliver food and medication directly into the stomach.1 In patients unable to tolerate gastric feeding, such as those with motility disorders and obstructions, these tubes are sometimes used to
Purpose. The gastrointestinal absorption sites of medications administered via postpyloric enteral feeding tubes were examined. Summary. Many issues must be considered when administering medications via the postpyloric route, including interactions with enteral feeds, additional toxicities, and the concern of whether the medication will be absorbed. Despite the potential clinical significance of this information, data regarding the gastrointestinal site of absorption for most medications are lacking. Gastrointestinal absorption sites for all drugs for which requests for information on absorption sites were received at our institution since 2008 (n = 124) were evaluated by reviewing the package insert, consulting tertiary references, conducting primary literature searches, or contacting the drug manufacturer. Seventy (56.5%) of the 124 drugs reviewed had information available regarding the site of absorption.
suction gastric contents. In the latter case, medication administration through the gastric tube should be avoided, as the medication will often be suctioned out before it can be absorbed.1,2 Additional routes of enteral access deliver contents directly into
Chelsey M. McIntyre, Pharm.D., is Clinical Pharmacy Specialist, Drug Information, Department of Pharmacy, and Heather M. Monk, Pharm.D., is Clinical Pharmacy Specialist, Neonatology, Department of Pharmacy, Children’s Hospital of Philadelphia, Philadelphia, PA. Address correspondence to Dr. McIntyre ([email protected]. edu).
Just 2 drugs required acid for absorption and thus should be administered only through the stomach, while 2 other drugs were found to bind extensively to tubing and should not be administered in this manner. For 3 drugs, increased absorption may occur when they are administered directly into the small bowel. Seven medications had decreased absorption when administered directly to the small bowel, and 10 drugs were clearly not absorbed when administered through either the duodenal or the jejunal route. Conclusion. The implications of absorption site should be considered for all patients receiving medications via postpyloric feeding tubes. Several medications cannot be administered through alternative routes because gastric acid is needed for their absorption, the medications may bind to the tubing, or drug absorption is altered at the intestinal site. Am J Health-Syst Pharm. 2014; 71:549-56
the small bowel. Nasoduodenal and nasojejunal tubes are passed through the nose into different portions of the small bowel. Routes of enteral access may also be placed surgically through the stomach wall and into both the stomach and jejunum, referred to as a gastrostomy/jejunostomy tube
The authors have declared no potential conflicts of interest. Copyright © 2014, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/14/0401-0549$06.00. DOI 10.2146/ajhp130597
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The Clinical Consultation section features articles that provide brief advice on how to handle specific drug therapy problems. All articles are based on a systematic review of the literature. The assistance of ASHP’s Section of Clinical Specialists and Scientists in soliciting Clinical Consultation submissions is acknowledged. Unsolicited submissions are also welcome.
(GJT). In this case, the lumen entering the stomach may sometimes be used for suctioning of gastric contents.1 Again, practitioners should be aware of the use of each lumen and avoid medication administration into the stomach when there are concerns about suctioning the medication before it can be absorbed.1,2 Patients with a GJT may also be able to receive food and medications either gastrically or jejunally. Concerns about postpyloric medication administration A few concerns exist regarding postpyloric medication administration. First, the indication for postpyloric medication administration often coincides with an indication for postpyloric enteral feeding. Because of this, patients are often receiving nutrition through the same tubing used to administer the medication. Interactions between the food and medication are concerning, and previously published literature, though limited, has evaluated and discussed these interactions.3-7 Another concern is the risk for additional adverse drug reactions (ADRs). Many liquid formulations of medications have osmolalities far exceeding that of the gastrointestinal tract, which can result in diarrhea, cramping, abdominal distention, and vomiting.8 These symptoms are usually attributable to inactive ingredients and excipients in the drug formulation. In fact, as many as 50% of patients experience ingredientrelated diarrhea when using enteral access tubes for medication admin550
istration.9 One example of a problematic ingredient in large quantities is propylene glycol.10 A number of sweeteners can also cause this issue, but sorbitol is the most common culprit. Its effects are cumulative and can worsen with increased exposure.2 An often unaddressed concern regarding postpyloric administration is whether the medication can be absorbed distal to the point at which it enters the gastrointestinal tract. Information is lacking regarding the intestinal absorption site of most medications. Since these data are not required by the Food and Drug Administration for drug development, they are often not available in the package insert or tertiary references. Unfortunately, alterations in drug absorption can produce a number of sequelae, including increased toxicity and treatment failure, which can be critical in a number of situations (e.g., treatment of infections or seizure disorders, use of medications with a narrow therapeutic range). Increased toxicity may occur due to a lack of degradation by stomach acid or decreased exposure to first-pass metabolism, leading to increased drug absorption.2 For instance, azathioprine absorption can increase by as much as 67% when administered directly into the jejunum. Because azathioprine is associated with toxicities such as bone marrow suppression and hepatotoxicity, as well as known pharmacogenomic variation, the clinical picture can be notably complicated by this alteration in absorption.11 An older approach for determining the site of absorption is based on the pH-partition hypothesis, which determines the site of drug absorption using the drug’s acid–base dissociation constant and the known pH of the gastrointestinal tract.12 However, this approach is not reliable due to its lack of consideration for the many other factors involved. Its limitations have been demonstrated previously, and it has fallen out of favor.12,13
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In order to obtain information regarding the site of medication absorption, it is often necessary to refer to the primary literature. Unfortunately, animal studies comprise the majority of the primary literature, and the results are difficult to extrapolate to the human gastrointestinal tract due to a number of differences among species.14 Another type of study available utilizes the in silico method. This method predicts the drug absorption site by utilizing a computer algorithm involving the properties of the human gastrointestinal tract and the drug molecule. While this method can provide valuable guidance, its accuracy has not been clinically validated.12 Finally, a small number of studies have been conducted in humans to evaluate absorption site. These studies are typically considered to be the gold standard for determining the likelihood of drug absorption at different entry points into the gastrointestinal tract.12,13 We conducted a literature review to determine the prevalence of existing absorption-site data for a specific list of medications administered in postpyloric feeding tubes and evaluated the relevance of absorption site in clinical care. Literature review At the Children’s Hospital of Philadelphia, a list of requests for information about drug absorption sites has been maintained since 2008. In order to address the recurring needs of the clinical staff at our institution, a project was undertaken to identify any existing data regarding the absorption sites for these medications. The following sources were researched sequentially to obtain these data: (1) package insert, (2) tertiary references (i.e., American Hospital Formulary System, Lexicomp, Clinical Pharmacology, and Micromedex), (3) primary literature (search conducted using PubMed), and (4)
CLINICAL CONSULTATION Medication absorption
information obtained from contact with the drug manufacturer. If information was found at any point in the research process, the process was considered complete for that medication, and no further research was conducted for the drug. The only exception to this was the instance in which information was found in the package insert. In these cases, the manufacturer was then contacted to confirm the interpretation of the data. The primary data point collected was the gastrointestinal absorption site of the medication. Additional information collected included the type of study conducted, medications that bind to tubing and should not be administered via a tube, a requirement for gastric acid for absorption, and known alterations in drug absorption due to administration at alternative sites. Summary of the literature findings A total of 124 medications were included for review. Of these, 16 (12.9%) had adequate information available in tertiary references. After review of the primary literature, contact with the manufacturer was still necessary for 54 (43.5%) medications (Table 1). After completion of the review, only 70 medications (56.5%) had information available regarding the site of absorption (3 came from nonvalidated in silico studies). Of these medications, the information and its implications varied. Just 2 medications (2.9%; aspirin and ferrous sulfate) required acid for absorption and thus should be administered only through the stomach, while 2 other medications (2.9%; cyclosporine and isotretinoin) were found to bind extensively to tubing and should not be administered in this manner. Data for 5 drugs (7.1%; azathioprine, ciprofloxacin, fluconazole, pravastatin, and zinc) indicated that increased absorption may occur when the drugs are administered
Table 1.
Acceptable Administration Routes for Specific Medications via Postpyloric Enteral Feeding Tubes Acceptable Administration Routes via Enteral Tubesa Drug
Duodenal
Jejunal
Abacavir15 Acarbose16 Acetaminophen17,18 Acetazolamide19 Acetylcysteine20,21 Acyclovir22,23 Alendronate24 Allopurinol25 Amlodipine26 Amoxicillin27 Ascorbic acid28,29 Aspirin30 Atenolol31 Atomoxetine32 Azathioprine11 Baclofen33 Bethanechol34 Bumetanide35 Bupropion36 Caffeine37,38 Calcium39 Carnitine40 Carvedilol41 Cefdinir42 Chlorambucil43 Chlorothiazide44 Ciprofloxacin5,45,46 Cisapride47 Citalopram48 Citric acid–sodium citrate49 Clarithromycin50 Clindamycin51 Clonazepam52 Cotrimoxazole53 Cyclosporine54 Dapsone55 Desloratadine56 Digoxin57 Docusate58 Enalapril59 Erythromycin60 Escitalopram61 Ezogabine62 Ferrous sulfate63 Fluconazole64-66 Fluoxetine67 Folic acid68,69 Furosemide70
Unknown Yesb Yes Unknown Unknown Unknown Unknown Yes Unknown Yes Yes Noc Unknown Unknown Yesd Partial Unknowne Yes Unknowne Yes Yes Yes Unknown Unknown Unknown Yes Yesd Unknown Unknown Yes Yes Unknown Unknown Unknown Nof Yes Unknown Yes Yesb Unknown Yes Unknown Unknown Partialc Yesd Unknown Yes Yes
Unknown Yesb Yes Unknown Unknown Unknown Unknown Partial Unknown Yes Yes Noc Unknown Unknown Yesd Unknown Unknowne Unknown Unknowne Yes Partial Yes Unknown Unknown Unknown Yes Yesd Unknown Unknown Yes Yes Unknown Unknown Unknown Nof Yes Unknown No Yesb Unknown No Unknown Unknown Noc Yesd Unknown No Yes
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Table 1 (continued)
Drug Gabapentin71 Glycopyrrolate72 Griseofulvin73 Guaifenesin74 Hydrochlorothiazide44 Hydrocortisone75 Hydromorphone76 Hydroxychloroquine77 Isotretinoin78 Lactobacillus79 Lamivudine80 Lamotrigine81 Lansoprazole82 Levetiracetam83 Levothyroxine84 Levofloxacin85 Linezolid86 Loperamide87 Lopinavir–ritonavir88,89 Lorazepam90 Magnesium91 Medium-chain triglyceride oil92,93 Mesalamine94 Metformin95 Methadone96 Methylphenidate97 Metoclopramide98 Metolazone99 Metoprolol100 Metronidazole101 Mexiletine102 Midazolam103 Morphine104 Mycophenolate105 Nadolol106 Neomycin107 Nystatin108 Olanzapine109 Omeprazole110 Oseltamivir111 Oxcarbazepine112 Paroxetine113 Pentobarbital114 Phenobarbital115 Phenytoin116,117 Phosphate118 Potassium119 Pravastatin120 Prednisone75 Pregabalin121 Propranolol122
Acceptable Administration Routes via Enteral Tubesa Duodenal Jejunal Yes Unknown Yes Unknown Yes Unknown Unknown Unknown Nof Yesb Unknown Unknown Unknown Yes Yes Yes Unknown Unknown Yes Yes Yes
Partial Unknown No Unknown Yes Unknown Unknown Unknown Nof Yesb Unknown Unknown Unknown Yes Yes Yes Unknown Unknown Partial Unknown Yes
Yes Yes Yes Unknown Unknown Unknown Unknown Yes Unknown Unknown Yesg Unknown Yes Unknown Yesb Yesb Unknown Yes Yes Yes Yesh Unknown Yes Yes Unknown Unknown Yesd Unknown Yes Yes
Yes Yes No Unknown Unknown Unknown Unknown Yes Unknown Unknown Yesg Unknown No Unknown Yesb Yesb Unknown Yes Yes Yes Yesh Unknown Yes No Unknown Unknown No Unknown Yes Yes
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directly into the small bowel. Seven medications (10%; allopurinol, baclofen, calcium, ferrous sulfate, gabapentin, lopinavir–ritonavir, and sirolimus) had decreased absorption when administered directly to the small bowel. Finally, 10 medications (14.3%) were clearly not absorbed when administered through either the duodenal or the jejunal route (Table 1). Discussion A number of factors must be considered before administering medications through alternative routes, including the increased risk for ADRs, interactions with enteral feeds, and the minimal data available regarding the gastrointestinal site of absorption of each medication. For example, phenytoin has decreased absorption when given via the jejunum, which could result in a seizure. While therapeutic drug monitoring may compensate for reduced phenytoin absorption, awareness of this risk is crucial to encourage the timely evaluation of drug levels.116,117 There is also potential for critical treatment failure in the patient awaiting heart transplantation with placement of a ventricular assist device (VAD). VADs induce platelet activation requiring antiplatelet therapy, including aspirin. A patient receiving aspirin via the duodenum or jejunum could risk treatment failure due to the lack of acid activation.152 In addition, administration through an alternative route can lead to an increase in the amount of drug absorbed and potentially result in subsequent ADRs, such as with azathioprine.11 There is a paucity of data regarding the site of absorption for most medications. The administration of a medication via a route in which it is poorly absorbed could lead to critical treatment failure. This is increasingly concerning in a patient with a GJT who could be subject to frequent route changes between gastric and jejunal administrations.
CLINICAL CONSULTATION Medication absorption
Table 1 (continued)
Drug Ramelteon123 Ramipril124 Ranitidine125-127 Rifampin86 Risperidone128 Senna129 Sertraline130 Sevelamer131 Sildenafil132 Sirolimus133 Spironolactone134 Sucralfate135 Tacrolimus136 Theophylline137 Tizanidine138 Tocopherol139 Topiramate140,141 Ursodiol142 Valproic acid143 Vigabatrin144,145 Voriconazole146 Warfarin147,148 Zidovudine149 Zinc150 Zonisamide151
Acceptable Administration Routes via Enteral Tubesa Duodenal Jejunal Unknown Yesg Yes Yes Unknown Yesb Unknown Yesb Yes Yes Yes Nob Yes Yesg Unknown Yes Yes Yes No Unknown Unknown Yes Unknown Unknownd Unknown
Unknown Unknowng Yes Yes Unknown Yesb Unknown Yesb Yes Partial Yes Nob Yes Yesg Unknown No Yes Yes No Unknown Unknown Yes Unknown Unknownd Unknown
a Unknown = exact absorption site is unknown and clinical judgment should be used, yes = the drug is known to be absorbed via the indicated route, partial = some absorption occurs at this site but the extent is unknown, no = there is a known problem with administering the drug via the indicated route. b Not systemically absorbed. c Requires acid for absorption. d May have increased absorption when gastric route is bypassed. e Absorption in small intestine. f Binds to tubing. g Based on in silico model with no clinical validation. h Suspension requires acid for absorption; utilize crushed tablet.
The results of this evaluation confirm that there is indeed a scarcity of published information on this topic, as 43.5% of medications had none available. Further, for those medications for which information was available, much of the data had to be gathered as unpublished data from the drug manufacturer. These results also indicate that the site of absorption is a valid consideration for use of these medications. For those medications that had available information, 34.4% required clinical consideration due to a lack of absorption through specific routes,
impracticality of administration via postpyloric feeding tubes, or alterations in absorption. Table 1 provides information on a number of medications, albeit only a fraction of approved enteral medications available in the United States, to help guide the selection of an appropriate administration route. In specific situations, alternative medications for which absorption-site information is available can be used. In situations where an alternative medication cannot be selected and absorption-site information is unknown, patients should be monitored closely for signs
of efficacy and toxicity as indicators of an alteration in absorption. The information presented here indicates a need for awareness of the possibility of altered absorption, increased ADRs, and treatment failure when medications are administered via a postpyloric route. Conclusion The implications of absorption site should be considered for all patients receiving medications via postpyloric feeding tubes. Several medications cannot be administered through alternative routes because gastric acid is needed for their absorption, the medications may bind to the tubing, or drug absorption is altered at the intestinal site.. References 1. Magnuson BL, Clifford TM, Hoskins LA et al. Enteral nutrition and drug administration, interactions, and complications. Nutr Clin Pract. 2005; 20:618-24. 2. Beckwith MC, Feddema SS, Barton RG, Graves C. A guide to drug therapy in patients with enteral feeding tubes: dosage form selection and administration methods. Hosp Pharm. 2004; 39:225-37. 3. Cutie AJ, Altman E, Lenkel L. Compatibility of enteral products with commonly employed drug additives. J Parenter Enteral Nutr. 1983; 7:186-91. 4. Fay MA, Sheth RD, Gidal BE. Oral absorption kinetics of levetiracetam: the effect of mixing with food or enteral nutrition formulas. Clin Ther. 2005; 27:594-8. 5. Healy DP, Brodbeck MC, Clendening CE. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996; 40:6-10. 6. Holtz L, Milton J, Sturek JK. Compatibility of medications with enteral feedings. J Parenter Enteral Nutr. 1987; 11:183-6. 7. Strom JG Jr, Miller SW. Stability of drugs with enteral nutrient formulas. DICP. 1990; 24:130-4. 8. Estoup M. Approaches and limitations of medication delivery in patients with enteral feeding tubes. Crit Care Nurse. 1994; 14:68-72,77-9. 9. Klang MG. Medicating tube-fed patients. Nursing. 1996; 26:18. 10. Shepherd MF, Felt-Gunderson PA. Diarrhea associated with lorazepam solution in a tube-fed patient. Nutr Clin Pract. 1996; 11:117-20. 11. Gervasio JM, Brown RO, Lima J et al. Sequential group trial to determine gastrointestinal site of absorption and
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systemic exposure of azathioprine. Dig Dis Sci. 2000; 45:1601-7. 12. Rouge N, Buri P, Doelker E. Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int J Pharm. 1996; 136:117-39. 13. Burton PS, Goodwin JT, Vidmar TJ et al. Predicting drug absorption: how nature made it a difficult problem. J Pharmacol Exp Ther. 2002; 303:889-95. 14. Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos. 1995; 16:351-80. 15. Data on file for gastrointestinal absorption of abacavir. Viiv Pharmaceuticals, Brentford, United Kingdom; 2013 May. 16. Acarbose. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 17. Kennedy JM, van Rij AM. Drug absorption from the small intestine in immediate postoperative patients. Br J Anaesth. 2006; 97:171-80. 18. Nelson EB, Abernethy DR, Greenblatt DJ et al. Paracetamol absorption from a feeding jejunostomy. Br J Clin Pharmacol. 1986; 22:111-3. 19. Data on file for the gastrointestinal absorption of acetazolamide. Taro Pharmaceuticals, Hawthorne, NY; 2010 Aug. 20. Acetylcysteine. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 21. Rodenstein D, DeCoster A, Gazzaniga A. Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders. Clin Pharmacokinet. 1978; 3:247-54. 22. Essell JH, Schroeder MT, Harman GS et al. Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998; 128:975-81. 23. Data on file for the gastrointestinal absorption of acyclovir. GlaxoSmithKline, Research Triangle Park, NC; 2010 Aug. 24. Data on file for the gastrointestinal absorption of alendronate. Merck, Whitehouse Station, NJ; 2007 Sep. 25. Schuster O, Haertel M, Hugemann B et al. [The clinical pharmacokinetics of allopurinol. 1. Allopurinol absorption sites and dose proportionality of allopurinol/oxipurinol bioavailability]. Arzneimittelforschung. 1985; 35:760-5. In German. 26. Data on file for the gastrointestinal absorption of amlodipine. Pfizer, New York; 2013 May. 27. Barr WH, Zola EM, Candler EL et al. Differential absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther. 1994; 56:279-85. 28. Graumlich JF, Ludden TM, ConryCantilena C et al. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm Res. 1997; 14:1133-9.
554
29. Mayersohn M. Ascorbic acid absorption in man—pharmacokinetic implications. Eur J Pharmacol. 1972; 19:140-2. 30. Graham DY, Smith JL. Aspirin and the stomach. Ann Intern Med. 1986; 104:390-8. 31. Data on file for the gastrointestinal absorption of atenolol. AstraZeneca Pharmaceuticals, Wilmington, DE; 2013 May. 32. Data on file for the gastrointestinal absorption of atomoxetine. Eli Lilly, Indianapolis; 2011 Nov. 33. Kochak GM, Rakhit A, Wagner WE et al. The pharmacokinetics of baclofen derived from intestinal infusion. Clin Pharmacol Ther. 1985; 38:251-7. 34. Data on file for the gastrointestinal absorption of bethanechol. Rising Pharmaceuticals, Allendale, NJ; 2010 Feb. 35. Mackie PH, Thomson MR, Levine DF et al. A comparison of the effect of frusemide and bumetanide on the diuretic response and fibrinolytic mechanism in man. Br J Clin Pharmacol. 1976; 3:613-9. 36. Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: pharmacokinetic and formulation considerations. Clin Ther. 2005; 27:1685-95. 37. Blanchard J, Sawers SJ. The absolute bioavailability of caffeine in man. Eur J Clin Pharmacol. 1983; 24:93-8. 38. Chvasta TE, Cooke AR. Emptying and absorption of caffeine from the human stomach. Gastroenterology. 1971; 61:83843. 39. Perez AV, Picotto G, Carpentieri AR et al. Minireview on regulation of intestinal calcium absorption. Emphasis on molecular mechanisms of transcellular pathway. Digestion. 2008; 77:22-34. 40. Carnitine. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 41. Data on file for the gastrointestinal absorption of carvedilol. GlaxoSmithKline, Research Triangle Park, NC; 2010 Aug. 42. Sakamoto H, Hirose T, Nakamoto S et al. Pharmacokinetics of FK482, a new orally active cephalosporin, in animals. J Antibiot. 1988; 41:1896-905. 43. Data on file for the gastrointestinal absorption of chlorambucil. Aspen Pharmaceuticals, LaLucia, South Africa; 2013 Jun. 44. Beermann B, Groschinsky-Grind M, Rosen A. Absorption, metabolism, and excretion of hydrochlorothiazide. Clin Pharmacol Ther. 1976; 19:531-7. 45. Yuk JH, Nightingale CH, Quintiliani R et al. Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition. Diagn Microbiol Infect Dis. 1990; 13:99-102. 46. Sahai J, Memish Z, Conway B. Ciprofloxacin pharmacokinetics after administration via a jejunostomy tube. J Antimicrob Chemother. 1991; 28:936-7. 47. Data on file for the gastrointestinal absorption of cisapride. Janssen-Ortho
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Pharmaceuticals, Titusville, NJ; 2013 Jun. 48. Data on file for the gastrointestinal absorption of citalopram. Forest Laboratories, St. Louis; 2013 May. 49. Fordtran JS, Rector FC Jr, Carter NW. The mechanisms of sodium absorption in the human small intestine. J Clin Invest. 1968; 47:884-900. 50. Clarithromycin—summary of product characteristics. Bordon, Hampshire, United Kingdom: Sandoz Limited; 2005. 51. Yang SH, Lee MG. Dose-independent pharmacokinetics of clindamycin after intravenous and oral administration to rats: contribution of gastric first-pass effect to low bioavailability. Int J Pharm. 2007; 332:17-23. 52. Data on file for the gastrointestinal absorption of clonazepam. Roche Pharmaceuticals, Nutley, NJ; 2010 Jul. 53. Data on file for the gastrointestinal absorption of cotrimoxazole. URL, 2013. 54. Data on file for the gastrointestinal absorption of cyclosporine. Novartis, Greensboro, NC; 2013 Jan. 55. Data on file for the gastrointestinal absorption of dapsone. Jacobus, Plainsboro, NJ; 2013 May. 56. Data on file for the gastrointestinal absorption of desloratadine. Merck, Whitehouse Station, NJ; 2011 Aug. 57. Digoxin. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 58. Docusate. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 59. Data on file for the gastrointestinal absorption of enalapril. Valeant Pharmaceuticals, Bridgewater, NJ; 2011 Dec. 60. Erythromycin. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 61. Data on file for the gastrointestinal absorption of escitalopram. Forest Laboratories, St. Louis; 2013 May. 62. Data on file for the gastrointestinal absorption of ezogabine. GlaxoSmithKline, Research Triangle Park, NC; 2013 May. 63. Ferrous sulfate. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 64. Data on file for the gastrointestinal absorption of fluconazole. Pfizer, Philadelphia; 2006 Nov. 65. Joe LA, Jacobs RA, Guglielmo BJ. Systemic absorption of oral fluconazole after gastrointestinal resection. J Antimicrob Chemother. 1994; 33:1070. Letter. 66. Pelz RK, Lipsett PA, Swoboda SM et al. Enteral fluconazole is well absorbed in critically ill surgical patients. Surgery. 2002; 131:534-40. 67. Data on file for the gastrointestinal absorption of fluoxetine. Eli Lilly, Indianapolis; 2013 May. 68. Folic acid. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically.
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69. Hepner GW, Booth CC, Cowan J et al. Absorption of crystalline folic acid in man. Lancet. 1968; 2:302-6. 70. Lee WI, Yoon WH, Shin WG et al. Pharmacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum. Biopharm Drug Dispos. 1997; 18:753-67. 71. Data on file for the gastrointestinal absorption of gabapentin. Pfizer, New York; 2005 Jul. 72. Rashid H, Long JD, Wadleigh RG. Management of secretions in esophageal cancer patients with glycopyrrolate. Ann Oncol. 1997; 8:198-9. 73. Griseofulvin. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 74. Kagan L, Lavy E, Hoffman A. Effect of mode of administration on guaifenesin pharmacokinetics and expectorant action in the rat model. Pulm Pharmacol Ther. 2009; 22:260-5. 75. Nakayama A, Eguchi O, Hatakeyama M et al. Different absorption behaviors among steroid hormones due to possible interaction with P-glycoprotein in the rat small intestine. Biol Pharm Bull. 1999; 22:535-8. 76. Data on file for the gastrointestinal absorption of hydromorphone. Abbott Pharmaceuticals, North Chicago, IL; 2007 Feb. 77. Data on file for the gastrointestinal absorption of hydroxychloroquine. Sanofiaventis, Bridgewater, NJ; 2007 Jan. 78. Data on file for the gastrointestinal absorption of isotretinoin. Mylan Pharmaceuticals, Canonsburg, PA; 2013 Aug. 79. Lactobacillus. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 80. Data on file for the gastrointestinal absorption of lamivudine. Viiv Pharmaceuticals, Brentford, United Kingdom; 2013 May. 81. Birnbaum AK, Kriel RL, Im Y et al. Relative bioavailability of lamotrigine chewable dispersible tablets administered rectally. Pharmacotherapy. 2001; 21:158-62. 82. Data on file for the gastrointestinal absorption of lansoprazole. Takeda, Deerfield, IL; 2013 Jun. 83. Stockis A, Sargentini-Maier ML, Otoul C et al. Assessment of levetiracetam bioavailability from targeted sites in the human intestine using remotely activated capsules and gamma scintigraphy: open-label, single-dose, randomized, four-way crossover study in healthy male volunteers. Clin Ther. 2010; 32:1813-21. 84. Levothyroxine. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 85. Reid J, Marciniuk D, Peloquin CA et al. Pharmacokinetics of antituberculosis medications delivered via percutaneous gastrojejunostomy tube. Chest. 121:281-4.
86. Data on file for the gastrointestinal absorption of linezolid. Pfizer, New York; 2007 Feb. 87. Data on file for the gastrointestinal absorption of loperamide. McNeil Consumer and Specialty Pharmaceuticals, Washington, PA; 2011 Dec. 88. Boffito M, Arnaudo I, Raiteri R et al. Clinical use of lopinavir/ritonavir in a salvage therapy setting: pharmacokinetics and pharmacodynamics. AIDS. 2002; 16:2081-3. 89. Kamimura M, Watanabe K, Kobayakawa M et al. Successful absorption of antiretroviral drugs after gastrojejunal bypass surgery following failure of therapy through a jejunal tube. Intern Med. 2009; 48:1103-4. 90. Data on file for the gastrointestinal absorption of lorazepam. Roxane, Columbus, OH; 2005 Apr. 91. Magnesium. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 92. Medium-chain triglyceride (MCT) oil. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 93. Data on file for the gastrointestinal absorption of MCT oil. Novartis Nutrition, St. Louis; 2008 Jan. 94. Data on file for the gastrointestinal absorption of mesalamine. Proctor & Gamble Pharmaceuticals, Cincinnati; 2013 May. 95. Vidon N, Chaussade S, Noel M et al. Metformin in the digestive tract. Diabetes Res Clin Pract. 1988; 4:223-9. 96. Data on file for the gastrointestinal absorption of methadone. Mallinckrodt, St. Louis; 2013 Jun. 97. Data on file for the gastrointestinal absorption of methylphenidate. Janssen Pharmaceuticals, Titusville, NJ; 2013 May. 98. Data on file for the gastrointestinal absorption of metoclopramide. Baxter, Deerfield, IL; 2013 May. 99. Data on file for the gastrointestinal absorption of metolazone. UCB Pharmaceuticals, Smyrna, GA; 2013 May. 100. Jobin G, Cortot A, Godbillon J et al. Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum. Br J Clin Pharmacol. 1985; 19(suppl 2):97S-105S. 101. Data on file for the gastrointestinal absorption of metronidazole. Pfizer, New York; 2013 May. 102. Data on file for the gastrointestinal absorption of mexiletine. Teva Pharmaceuticals, Tikva, Israel; 2013 May. 103. Jamei M, Yang J, Turner D et al. A novel physiologically-based mechanistic model for predicting oral drug absorption: the advanced dissolution, absorption, and metabolism (ADAM) model. Poster presented at the Fourth World Conference on Drug Absorption, Transport and Delivery. Kanazawa, Japan; 2007.
104. Okura T, Ozawa T, Ibe M et al. Effects of repeated morphine treatment on the antinociceptive effects, intestinal absorption, and efflux from intestinal epithelial cells of morphine. Biol Pharm Bull. 2009; 32:1571-5. 105. Bullingham R, Monroe S, Nicholls A et al. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clin Pharmacol. 1996; 36:315-24. 106. Data on file for the gastrointestinal absorption of nadolol. King Pharmaceuticals (Pfizer), Bristol, TN; 2013 May. 107. Neomycin. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 108. Data on file for the gastrointestinal absorption of nystatin. Taro Pharmaceuticals, Hawthorne, NY; 2013 Apr. 109. Data on file for the gastrointestinal absorption of olanzapine. Eli Lilly, Indianapolis; 2013 May. 110. Phillips JO, Olsen KM, Rebuck JA et al. A randomized, pharmacokinetic and pharmacodynamic, cross-over study of duodenal or jejunal administration compared to nasogastric administration of omeprazole suspension in patients at risk for stress ulcers. Am J Gastroenterol. 2001; 96:367-72. 111. Ariano RE, Sitar DS, Zelenitsky SA et al. Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza. CMAJ. 2010; 182:357-63. 112. Data on file for the gastrointestinal absorption of oxcarbazepine. Novartis, St. Louis; 2013 Jun. 113. Data on file for the gastrointestinal absorption of paroxetine. GlaxoSmithKline, Research Triangle Park, NC; 2013 Jun. 114. Data on file for the gastrointestinal absorption of pentobarbital. Lundbeck Pharmaceuticals, Deerfield, IL; 2013 May. 115. Tanaka C, Yagi H, Sakamoto M et al. Decreased phenobarbital absorption with charcoal administration for chronic renal failure. Ann Pharmacother. 2004; 38:73-6. 116. El-Darouti MA, El Nabarawy E, AbdelHalim MR et al. Phenytoin absorption in epidermolysis bullosa. Egypt J Dermatol Androl. 2009; 29:25-32. 117. Treiman DM, Woodbury DM. Phenytoin: absorption, distribution, and excretion. In: Levy RH, Mattson RH, Meldrum BS, eds. Antiepileptic drugs, 4th ed. New York: Raven; 1995:301-14. 118. Scharrer E. Phosphate absorption at different intestinal sites in the developing lamb. Q J Exp Physiol. 1985; 70:615-21. 119. Hurwitz S, Clarkson TW, Bar A. Intestinal absorption of sodium and potassium in the laying fowl. J Nutr. 1970; 100:1181-7. 120. Triscari J, Swanson BN, Willard DA et al. Steady state serum concentrations of pravastatin and digoxin when given in
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combination. Br J Clin Pharmacol. 1993; 36:263-5. 121. Bockbrader HN, Wesche D, Miller R et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010; 49:661-9. 122. Buch A, Barr WH. Absorption of propranolol in humans following oral, jejunal, and ileal administration. Pharm Res. 1998; 15:953-7. 123. Data on file for the gastrointestinal absorption of ramelteon. Takeda Pharmaceueticals, Deerfield, IL; 2008 Feb. 124. Levitt DG, Schoemaker RC. Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat. BMC Clin Pharmacol. 2006; 6:1. 125. Data on file for the gastrointestinal absorption of ranitidine. GlaxoWellcome, London, England; 2000 Mar. 126. Gramatte T, el Desoky E, Klotz U. Sitedependent small intestinal absorption of ranitidine. Eur J Clin Pharmacol. 1994; 46:253-9. 127. Williams MF, Dukes GE, Heizer W et al. Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine. Pharm Res. 1992; 9:1190-4. 128. Data on file for the gastrointestinal absorption of risperidone. Janssen Pharmaceuticals, Titusville, NJ; 2013 May. 129. Senna. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 130. Data on file for the gastrointestinal absorption of sertraline. Pfizer, New York; 2003 Mar.
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131. Data on file for the gastrointestinal absorption of sevelamer. Sanofi-Aventis, Bridgewater, NJ; 2013 Jan. 132. Data on file for the gastrointestinal absorption of sildenafil. Pfizer, New York; 2008 Dec. 133. Data on file for the gastrointestinal absorption of sirolimus. Wyeth Pharmaceuticals, Philadelphia; 2008 Dec. 134. Data on file for the gastrointestinal absorption of spironolactone. Searle, Skokie, IL; 2000 Nov. 135. Data on file for the gastrointestinal absorption of sucralfate. Aptalis Pharma, Bridgewater, NJ; 2013 Jun. 136. Data on file for the gastrointestinal absorption of tacrolimus. Astellas Pharmaceuticals, Northbrook, IL; 2013 May. 137. Kadono K, Yokoe J, Ogawara K et al. Analysis and prediction of absorption behavior for theophylline orally administered as powders based on gastrointestinal-transit-absorption (Gita) model. Drug Metab Pharmacokinet. 2002; 17:307-15. 138. Data on file for the gastrointestinal absorption of tizanidine. Acorda Therapeutics, Ardsley, NY; 2013 May. 139. Kayden HJ, Traber MG. Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res. 1993; 34:343-58. 140. Data on file for the gastrointestinal absorption of topiramate. Janssen Pharmaceuticals, Titusville, NJ; 2013 May. 141. Limited KHK: report on deliberation results for topiramate, in evaluation and licensing division PaFSB (ed). Tokyo, Japan: Takeda; 2007:22. 142. Ursodiol. Clinical Pharmacology [Internet database]. Tampa: Gold Standard; 2013. Updated periodically.
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143. Data on file for the gastrointestinal absorption of valproic acid. Abbvie, Chicago; 2013 May. 144. Data on file for the gastrointestinal absorption of vigabatrin. Lundbeck Pharmaceuticals, Deerfield, IL; 2011 Mar. 145. Abbot EL, Grenade DS, Kennedy DJ et al. Vigabatrin transport across the human intestinal epithelial (Caco-2) brushborder membrane is via the H+-coupled amino-acid transporter hPAT1. Br J Pharmacol. 2006; 147:298-306. 146. Data on file for the gastrointestinal absorption of voriconazole. Pfizer, New York; 2011 Dec. 147. Kearns PJ Jr, O’Reilly RA. Bioavailability of warfarin in a patient with severe short bowel syndrome. J Parenter Enteral Nutr. 1986; 10:100-1. 148. Lutomski DM, LaFrance RJ, Bower RH et al. Warfarin absorption after massive small bowel resection. Am J Gastroenterol. 1985; 80:99-102. 149. Data on file for the gastrointestinal absorption of zidovudine. GlaxoSmithKline, Research Triangle Park, NC; 2013 May. 150. Neve J, Hanocq M, Peretz A et al. Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation. Eur J Drug Metab Pharmacokinet. 1991; 16:315-23. 151. Data on file for the gastrointestinal absorption of zonisamide. Eisai, Woodcliff Lake, NJ; 2013 May. 152. Ashbrook M, Walenga JM, Schwartz J et al. Left ventricular assist device-induced coagulation and platelet activation and effect of the current anticoagulant therapy regimen. Clin Appl Thromb Hemost. 2013; 19:249-55.
C L I N I C A L C O N S U LTAT I O N
Medication absorption considerations in patients with postpyloric enteral feeding tubes Chelsey M. McIntyre and Heather M. Monk
M
edication administration via the gastrointestinal tract is not straightforward in all patients. There is an occasional need to bypass the stomach with an enteral feeding tube (i.e., postpyloric feeding tube), allowing for administration of both food and medication directly into the small bowel. Acutely ill patients may require a postpyloric feeding tube due to acute gastrointestinal discomfort or vomiting. Chronically ill patients may require the placement of such a tube for a variety of reasons, such as delayed gastric emptying (gastroparesis), chronic nausea or vomiting, and severe reflux.1 Routes of enteral access Many different routes of enteral access may be used for the postpyloric administration of food and medications. Routes of enteral access are described by the anatomical site of insertion and the site of termination. Nasogastric tubes and gastrostomy tubes deliver food and medication directly into the stomach.1 In patients unable to tolerate gastric feeding, such as those with motility disorders and obstructions, these tubes are sometimes used to
Purpose. The gastrointestinal absorption sites of medications administered via postpyloric enteral feeding tubes were examined. Summary. Many issues must be considered when administering medications via the postpyloric route, including interactions with enteral feeds, additional toxicities, and the concern of whether the medication will be absorbed. Despite the potential clinical significance of this information, data regarding the gastrointestinal site of absorption for most medications are lacking. Gastrointestinal absorption sites for all drugs for which requests for information on absorption sites were received at our institution since 2008 (n = 124) were evaluated by reviewing the package insert, consulting tertiary references, conducting primary literature searches, or contacting the drug manufacturer. Seventy (56.5%) of the 124 drugs reviewed had information available regarding the site of absorption.
suction gastric contents. In the latter case, medication administration through the gastric tube should be avoided, as the medication will often be suctioned out before it can be absorbed.1,2 Additional routes of enteral access deliver contents directly into
Chelsey M. McIntyre, Pharm.D., is Clinical Pharmacy Specialist, Drug Information, Department of Pharmacy, and Heather M. Monk, Pharm.D., is Clinical Pharmacy Specialist, Neonatology, Department of Pharmacy, Children’s Hospital of Philadelphia, Philadelphia, PA. Address correspondence to Dr. McIntyre ([email protected]. edu).
Just 2 drugs required acid for absorption and thus should be administered only through the stomach, while 2 other drugs were found to bind extensively to tubing and should not be administered in this manner. For 3 drugs, increased absorption may occur when they are administered directly into the small bowel. Seven medications had decreased absorption when administered directly to the small bowel, and 10 drugs were clearly not absorbed when administered through either the duodenal or the jejunal route. Conclusion. The implications of absorption site should be considered for all patients receiving medications via postpyloric feeding tubes. Several medications cannot be administered through alternative routes because gastric acid is needed for their absorption, the medications may bind to the tubing, or drug absorption is altered at the intestinal site. Am J Health-Syst Pharm. 2014; 71:549-56
the small bowel. Nasoduodenal and nasojejunal tubes are passed through the nose into different portions of the small bowel. Routes of enteral access may also be placed surgically through the stomach wall and into both the stomach and jejunum, referred to as a gastrostomy/jejunostomy tube
The authors have declared no potential conflicts of interest. Copyright © 2014, American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/14/0401-0549$06.00. DOI 10.2146/ajhp130597
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The Clinical Consultation section features articles that provide brief advice on how to handle specific drug therapy problems. All articles are based on a systematic review of the literature. The assistance of ASHP’s Section of Clinical Specialists and Scientists in soliciting Clinical Consultation submissions is acknowledged. Unsolicited submissions are also welcome.
(GJT). In this case, the lumen entering the stomach may sometimes be used for suctioning of gastric contents.1 Again, practitioners should be aware of the use of each lumen and avoid medication administration into the stomach when there are concerns about suctioning the medication before it can be absorbed.1,2 Patients with a GJT may also be able to receive food and medications either gastrically or jejunally. Concerns about postpyloric medication administration A few concerns exist regarding postpyloric medication administration. First, the indication for postpyloric medication administration often coincides with an indication for postpyloric enteral feeding. Because of this, patients are often receiving nutrition through the same tubing used to administer the medication. Interactions between the food and medication are concerning, and previously published literature, though limited, has evaluated and discussed these interactions.3-7 Another concern is the risk for additional adverse drug reactions (ADRs). Many liquid formulations of medications have osmolalities far exceeding that of the gastrointestinal tract, which can result in diarrhea, cramping, abdominal distention, and vomiting.8 These symptoms are usually attributable to inactive ingredients and excipients in the drug formulation. In fact, as many as 50% of patients experience ingredientrelated diarrhea when using enteral access tubes for medication admin550
istration.9 One example of a problematic ingredient in large quantities is propylene glycol.10 A number of sweeteners can also cause this issue, but sorbitol is the most common culprit. Its effects are cumulative and can worsen with increased exposure.2 An often unaddressed concern regarding postpyloric administration is whether the medication can be absorbed distal to the point at which it enters the gastrointestinal tract. Information is lacking regarding the intestinal absorption site of most medications. Since these data are not required by the Food and Drug Administration for drug development, they are often not available in the package insert or tertiary references. Unfortunately, alterations in drug absorption can produce a number of sequelae, including increased toxicity and treatment failure, which can be critical in a number of situations (e.g., treatment of infections or seizure disorders, use of medications with a narrow therapeutic range). Increased toxicity may occur due to a lack of degradation by stomach acid or decreased exposure to first-pass metabolism, leading to increased drug absorption.2 For instance, azathioprine absorption can increase by as much as 67% when administered directly into the jejunum. Because azathioprine is associated with toxicities such as bone marrow suppression and hepatotoxicity, as well as known pharmacogenomic variation, the clinical picture can be notably complicated by this alteration in absorption.11 An older approach for determining the site of absorption is based on the pH-partition hypothesis, which determines the site of drug absorption using the drug’s acid–base dissociation constant and the known pH of the gastrointestinal tract.12 However, this approach is not reliable due to its lack of consideration for the many other factors involved. Its limitations have been demonstrated previously, and it has fallen out of favor.12,13
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In order to obtain information regarding the site of medication absorption, it is often necessary to refer to the primary literature. Unfortunately, animal studies comprise the majority of the primary literature, and the results are difficult to extrapolate to the human gastrointestinal tract due to a number of differences among species.14 Another type of study available utilizes the in silico method. This method predicts the drug absorption site by utilizing a computer algorithm involving the properties of the human gastrointestinal tract and the drug molecule. While this method can provide valuable guidance, its accuracy has not been clinically validated.12 Finally, a small number of studies have been conducted in humans to evaluate absorption site. These studies are typically considered to be the gold standard for determining the likelihood of drug absorption at different entry points into the gastrointestinal tract.12,13 We conducted a literature review to determine the prevalence of existing absorption-site data for a specific list of medications administered in postpyloric feeding tubes and evaluated the relevance of absorption site in clinical care. Literature review At the Children’s Hospital of Philadelphia, a list of requests for information about drug absorption sites has been maintained since 2008. In order to address the recurring needs of the clinical staff at our institution, a project was undertaken to identify any existing data regarding the absorption sites for these medications. The following sources were researched sequentially to obtain these data: (1) package insert, (2) tertiary references (i.e., American Hospital Formulary System, Lexicomp, Clinical Pharmacology, and Micromedex), (3) primary literature (search conducted using PubMed), and (4)
CLINICAL CONSULTATION Medication absorption
information obtained from contact with the drug manufacturer. If information was found at any point in the research process, the process was considered complete for that medication, and no further research was conducted for the drug. The only exception to this was the instance in which information was found in the package insert. In these cases, the manufacturer was then contacted to confirm the interpretation of the data. The primary data point collected was the gastrointestinal absorption site of the medication. Additional information collected included the type of study conducted, medications that bind to tubing and should not be administered via a tube, a requirement for gastric acid for absorption, and known alterations in drug absorption due to administration at alternative sites. Summary of the literature findings A total of 124 medications were included for review. Of these, 16 (12.9%) had adequate information available in tertiary references. After review of the primary literature, contact with the manufacturer was still necessary for 54 (43.5%) medications (Table 1). After completion of the review, only 70 medications (56.5%) had information available regarding the site of absorption (3 came from nonvalidated in silico studies). Of these medications, the information and its implications varied. Just 2 medications (2.9%; aspirin and ferrous sulfate) required acid for absorption and thus should be administered only through the stomach, while 2 other medications (2.9%; cyclosporine and isotretinoin) were found to bind extensively to tubing and should not be administered in this manner. Data for 5 drugs (7.1%; azathioprine, ciprofloxacin, fluconazole, pravastatin, and zinc) indicated that increased absorption may occur when the drugs are administered
Table 1.
Acceptable Administration Routes for Specific Medications via Postpyloric Enteral Feeding Tubes Acceptable Administration Routes via Enteral Tubesa Drug
Duodenal
Jejunal
Abacavir15 Acarbose16 Acetaminophen17,18 Acetazolamide19 Acetylcysteine20,21 Acyclovir22,23 Alendronate24 Allopurinol25 Amlodipine26 Amoxicillin27 Ascorbic acid28,29 Aspirin30 Atenolol31 Atomoxetine32 Azathioprine11 Baclofen33 Bethanechol34 Bumetanide35 Bupropion36 Caffeine37,38 Calcium39 Carnitine40 Carvedilol41 Cefdinir42 Chlorambucil43 Chlorothiazide44 Ciprofloxacin5,45,46 Cisapride47 Citalopram48 Citric acid–sodium citrate49 Clarithromycin50 Clindamycin51 Clonazepam52 Cotrimoxazole53 Cyclosporine54 Dapsone55 Desloratadine56 Digoxin57 Docusate58 Enalapril59 Erythromycin60 Escitalopram61 Ezogabine62 Ferrous sulfate63 Fluconazole64-66 Fluoxetine67 Folic acid68,69 Furosemide70
Unknown Yesb Yes Unknown Unknown Unknown Unknown Yes Unknown Yes Yes Noc Unknown Unknown Yesd Partial Unknowne Yes Unknowne Yes Yes Yes Unknown Unknown Unknown Yes Yesd Unknown Unknown Yes Yes Unknown Unknown Unknown Nof Yes Unknown Yes Yesb Unknown Yes Unknown Unknown Partialc Yesd Unknown Yes Yes
Unknown Yesb Yes Unknown Unknown Unknown Unknown Partial Unknown Yes Yes Noc Unknown Unknown Yesd Unknown Unknowne Unknown Unknowne Yes Partial Yes Unknown Unknown Unknown Yes Yesd Unknown Unknown Yes Yes Unknown Unknown Unknown Nof Yes Unknown No Yesb Unknown No Unknown Unknown Noc Yesd Unknown No Yes
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Table 1 (continued)
Drug Gabapentin71 Glycopyrrolate72 Griseofulvin73 Guaifenesin74 Hydrochlorothiazide44 Hydrocortisone75 Hydromorphone76 Hydroxychloroquine77 Isotretinoin78 Lactobacillus79 Lamivudine80 Lamotrigine81 Lansoprazole82 Levetiracetam83 Levothyroxine84 Levofloxacin85 Linezolid86 Loperamide87 Lopinavir–ritonavir88,89 Lorazepam90 Magnesium91 Medium-chain triglyceride oil92,93 Mesalamine94 Metformin95 Methadone96 Methylphenidate97 Metoclopramide98 Metolazone99 Metoprolol100 Metronidazole101 Mexiletine102 Midazolam103 Morphine104 Mycophenolate105 Nadolol106 Neomycin107 Nystatin108 Olanzapine109 Omeprazole110 Oseltamivir111 Oxcarbazepine112 Paroxetine113 Pentobarbital114 Phenobarbital115 Phenytoin116,117 Phosphate118 Potassium119 Pravastatin120 Prednisone75 Pregabalin121 Propranolol122
Acceptable Administration Routes via Enteral Tubesa Duodenal Jejunal Yes Unknown Yes Unknown Yes Unknown Unknown Unknown Nof Yesb Unknown Unknown Unknown Yes Yes Yes Unknown Unknown Yes Yes Yes
Partial Unknown No Unknown Yes Unknown Unknown Unknown Nof Yesb Unknown Unknown Unknown Yes Yes Yes Unknown Unknown Partial Unknown Yes
Yes Yes Yes Unknown Unknown Unknown Unknown Yes Unknown Unknown Yesg Unknown Yes Unknown Yesb Yesb Unknown Yes Yes Yes Yesh Unknown Yes Yes Unknown Unknown Yesd Unknown Yes Yes
Yes Yes No Unknown Unknown Unknown Unknown Yes Unknown Unknown Yesg Unknown No Unknown Yesb Yesb Unknown Yes Yes Yes Yesh Unknown Yes No Unknown Unknown No Unknown Yes Yes
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directly into the small bowel. Seven medications (10%; allopurinol, baclofen, calcium, ferrous sulfate, gabapentin, lopinavir–ritonavir, and sirolimus) had decreased absorption when administered directly to the small bowel. Finally, 10 medications (14.3%) were clearly not absorbed when administered through either the duodenal or the jejunal route (Table 1). Discussion A number of factors must be considered before administering medications through alternative routes, including the increased risk for ADRs, interactions with enteral feeds, and the minimal data available regarding the gastrointestinal site of absorption of each medication. For example, phenytoin has decreased absorption when given via the jejunum, which could result in a seizure. While therapeutic drug monitoring may compensate for reduced phenytoin absorption, awareness of this risk is crucial to encourage the timely evaluation of drug levels.116,117 There is also potential for critical treatment failure in the patient awaiting heart transplantation with placement of a ventricular assist device (VAD). VADs induce platelet activation requiring antiplatelet therapy, including aspirin. A patient receiving aspirin via the duodenum or jejunum could risk treatment failure due to the lack of acid activation.152 In addition, administration through an alternative route can lead to an increase in the amount of drug absorbed and potentially result in subsequent ADRs, such as with azathioprine.11 There is a paucity of data regarding the site of absorption for most medications. The administration of a medication via a route in which it is poorly absorbed could lead to critical treatment failure. This is increasingly concerning in a patient with a GJT who could be subject to frequent route changes between gastric and jejunal administrations.
CLINICAL CONSULTATION Medication absorption
Table 1 (continued)
Drug Ramelteon123 Ramipril124 Ranitidine125-127 Rifampin86 Risperidone128 Senna129 Sertraline130 Sevelamer131 Sildenafil132 Sirolimus133 Spironolactone134 Sucralfate135 Tacrolimus136 Theophylline137 Tizanidine138 Tocopherol139 Topiramate140,141 Ursodiol142 Valproic acid143 Vigabatrin144,145 Voriconazole146 Warfarin147,148 Zidovudine149 Zinc150 Zonisamide151
Acceptable Administration Routes via Enteral Tubesa Duodenal Jejunal Unknown Yesg Yes Yes Unknown Yesb Unknown Yesb Yes Yes Yes Nob Yes Yesg Unknown Yes Yes Yes No Unknown Unknown Yes Unknown Unknownd Unknown
Unknown Unknowng Yes Yes Unknown Yesb Unknown Yesb Yes Partial Yes Nob Yes Yesg Unknown No Yes Yes No Unknown Unknown Yes Unknown Unknownd Unknown
a Unknown = exact absorption site is unknown and clinical judgment should be used, yes = the drug is known to be absorbed via the indicated route, partial = some absorption occurs at this site but the extent is unknown, no = there is a known problem with administering the drug via the indicated route. b Not systemically absorbed. c Requires acid for absorption. d May have increased absorption when gastric route is bypassed. e Absorption in small intestine. f Binds to tubing. g Based on in silico model with no clinical validation. h Suspension requires acid for absorption; utilize crushed tablet.
The results of this evaluation confirm that there is indeed a scarcity of published information on this topic, as 43.5% of medications had none available. Further, for those medications for which information was available, much of the data had to be gathered as unpublished data from the drug manufacturer. These results also indicate that the site of absorption is a valid consideration for use of these medications. For those medications that had available information, 34.4% required clinical consideration due to a lack of absorption through specific routes,
impracticality of administration via postpyloric feeding tubes, or alterations in absorption. Table 1 provides information on a number of medications, albeit only a fraction of approved enteral medications available in the United States, to help guide the selection of an appropriate administration route. In specific situations, alternative medications for which absorption-site information is available can be used. In situations where an alternative medication cannot be selected and absorption-site information is unknown, patients should be monitored closely for signs
of efficacy and toxicity as indicators of an alteration in absorption. The information presented here indicates a need for awareness of the possibility of altered absorption, increased ADRs, and treatment failure when medications are administered via a postpyloric route. Conclusion The implications of absorption site should be considered for all patients receiving medications via postpyloric feeding tubes. Several medications cannot be administered through alternative routes because gastric acid is needed for their absorption, the medications may bind to the tubing, or drug absorption is altered at the intestinal site.. References 1. Magnuson BL, Clifford TM, Hoskins LA et al. Enteral nutrition and drug administration, interactions, and complications. Nutr Clin Pract. 2005; 20:618-24. 2. Beckwith MC, Feddema SS, Barton RG, Graves C. A guide to drug therapy in patients with enteral feeding tubes: dosage form selection and administration methods. Hosp Pharm. 2004; 39:225-37. 3. Cutie AJ, Altman E, Lenkel L. Compatibility of enteral products with commonly employed drug additives. J Parenter Enteral Nutr. 1983; 7:186-91. 4. Fay MA, Sheth RD, Gidal BE. Oral absorption kinetics of levetiracetam: the effect of mixing with food or enteral nutrition formulas. Clin Ther. 2005; 27:594-8. 5. Healy DP, Brodbeck MC, Clendening CE. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996; 40:6-10. 6. Holtz L, Milton J, Sturek JK. Compatibility of medications with enteral feedings. J Parenter Enteral Nutr. 1987; 11:183-6. 7. Strom JG Jr, Miller SW. Stability of drugs with enteral nutrient formulas. DICP. 1990; 24:130-4. 8. Estoup M. Approaches and limitations of medication delivery in patients with enteral feeding tubes. Crit Care Nurse. 1994; 14:68-72,77-9. 9. Klang MG. Medicating tube-fed patients. Nursing. 1996; 26:18. 10. Shepherd MF, Felt-Gunderson PA. Diarrhea associated with lorazepam solution in a tube-fed patient. Nutr Clin Pract. 1996; 11:117-20. 11. Gervasio JM, Brown RO, Lima J et al. Sequential group trial to determine gastrointestinal site of absorption and
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systemic exposure of azathioprine. Dig Dis Sci. 2000; 45:1601-7. 12. Rouge N, Buri P, Doelker E. Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int J Pharm. 1996; 136:117-39. 13. Burton PS, Goodwin JT, Vidmar TJ et al. Predicting drug absorption: how nature made it a difficult problem. J Pharmacol Exp Ther. 2002; 303:889-95. 14. Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos. 1995; 16:351-80. 15. Data on file for gastrointestinal absorption of abacavir. Viiv Pharmaceuticals, Brentford, United Kingdom; 2013 May. 16. Acarbose. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 17. Kennedy JM, van Rij AM. Drug absorption from the small intestine in immediate postoperative patients. Br J Anaesth. 2006; 97:171-80. 18. Nelson EB, Abernethy DR, Greenblatt DJ et al. Paracetamol absorption from a feeding jejunostomy. Br J Clin Pharmacol. 1986; 22:111-3. 19. Data on file for the gastrointestinal absorption of acetazolamide. Taro Pharmaceuticals, Hawthorne, NY; 2010 Aug. 20. Acetylcysteine. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 21. Rodenstein D, DeCoster A, Gazzaniga A. Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders. Clin Pharmacokinet. 1978; 3:247-54. 22. Essell JH, Schroeder MT, Harman GS et al. Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998; 128:975-81. 23. Data on file for the gastrointestinal absorption of acyclovir. GlaxoSmithKline, Research Triangle Park, NC; 2010 Aug. 24. Data on file for the gastrointestinal absorption of alendronate. Merck, Whitehouse Station, NJ; 2007 Sep. 25. Schuster O, Haertel M, Hugemann B et al. [The clinical pharmacokinetics of allopurinol. 1. Allopurinol absorption sites and dose proportionality of allopurinol/oxipurinol bioavailability]. Arzneimittelforschung. 1985; 35:760-5. In German. 26. Data on file for the gastrointestinal absorption of amlodipine. Pfizer, New York; 2013 May. 27. Barr WH, Zola EM, Candler EL et al. Differential absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther. 1994; 56:279-85. 28. Graumlich JF, Ludden TM, ConryCantilena C et al. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm Res. 1997; 14:1133-9.
554
29. Mayersohn M. Ascorbic acid absorption in man—pharmacokinetic implications. Eur J Pharmacol. 1972; 19:140-2. 30. Graham DY, Smith JL. Aspirin and the stomach. Ann Intern Med. 1986; 104:390-8. 31. Data on file for the gastrointestinal absorption of atenolol. AstraZeneca Pharmaceuticals, Wilmington, DE; 2013 May. 32. Data on file for the gastrointestinal absorption of atomoxetine. Eli Lilly, Indianapolis; 2011 Nov. 33. Kochak GM, Rakhit A, Wagner WE et al. The pharmacokinetics of baclofen derived from intestinal infusion. Clin Pharmacol Ther. 1985; 38:251-7. 34. Data on file for the gastrointestinal absorption of bethanechol. Rising Pharmaceuticals, Allendale, NJ; 2010 Feb. 35. Mackie PH, Thomson MR, Levine DF et al. A comparison of the effect of frusemide and bumetanide on the diuretic response and fibrinolytic mechanism in man. Br J Clin Pharmacol. 1976; 3:613-9. 36. Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: pharmacokinetic and formulation considerations. Clin Ther. 2005; 27:1685-95. 37. Blanchard J, Sawers SJ. The absolute bioavailability of caffeine in man. Eur J Clin Pharmacol. 1983; 24:93-8. 38. Chvasta TE, Cooke AR. Emptying and absorption of caffeine from the human stomach. Gastroenterology. 1971; 61:83843. 39. Perez AV, Picotto G, Carpentieri AR et al. Minireview on regulation of intestinal calcium absorption. Emphasis on molecular mechanisms of transcellular pathway. Digestion. 2008; 77:22-34. 40. Carnitine. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 41. Data on file for the gastrointestinal absorption of carvedilol. GlaxoSmithKline, Research Triangle Park, NC; 2010 Aug. 42. Sakamoto H, Hirose T, Nakamoto S et al. Pharmacokinetics of FK482, a new orally active cephalosporin, in animals. J Antibiot. 1988; 41:1896-905. 43. Data on file for the gastrointestinal absorption of chlorambucil. Aspen Pharmaceuticals, LaLucia, South Africa; 2013 Jun. 44. Beermann B, Groschinsky-Grind M, Rosen A. Absorption, metabolism, and excretion of hydrochlorothiazide. Clin Pharmacol Ther. 1976; 19:531-7. 45. Yuk JH, Nightingale CH, Quintiliani R et al. Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition. Diagn Microbiol Infect Dis. 1990; 13:99-102. 46. Sahai J, Memish Z, Conway B. Ciprofloxacin pharmacokinetics after administration via a jejunostomy tube. J Antimicrob Chemother. 1991; 28:936-7. 47. Data on file for the gastrointestinal absorption of cisapride. Janssen-Ortho
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
Pharmaceuticals, Titusville, NJ; 2013 Jun. 48. Data on file for the gastrointestinal absorption of citalopram. Forest Laboratories, St. Louis; 2013 May. 49. Fordtran JS, Rector FC Jr, Carter NW. The mechanisms of sodium absorption in the human small intestine. J Clin Invest. 1968; 47:884-900. 50. Clarithromycin—summary of product characteristics. Bordon, Hampshire, United Kingdom: Sandoz Limited; 2005. 51. Yang SH, Lee MG. Dose-independent pharmacokinetics of clindamycin after intravenous and oral administration to rats: contribution of gastric first-pass effect to low bioavailability. Int J Pharm. 2007; 332:17-23. 52. Data on file for the gastrointestinal absorption of clonazepam. Roche Pharmaceuticals, Nutley, NJ; 2010 Jul. 53. Data on file for the gastrointestinal absorption of cotrimoxazole. URL, 2013. 54. Data on file for the gastrointestinal absorption of cyclosporine. Novartis, Greensboro, NC; 2013 Jan. 55. Data on file for the gastrointestinal absorption of dapsone. Jacobus, Plainsboro, NJ; 2013 May. 56. Data on file for the gastrointestinal absorption of desloratadine. Merck, Whitehouse Station, NJ; 2011 Aug. 57. Digoxin. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 58. Docusate. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 59. Data on file for the gastrointestinal absorption of enalapril. Valeant Pharmaceuticals, Bridgewater, NJ; 2011 Dec. 60. Erythromycin. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 61. Data on file for the gastrointestinal absorption of escitalopram. Forest Laboratories, St. Louis; 2013 May. 62. Data on file for the gastrointestinal absorption of ezogabine. GlaxoSmithKline, Research Triangle Park, NC; 2013 May. 63. Ferrous sulfate. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 64. Data on file for the gastrointestinal absorption of fluconazole. Pfizer, Philadelphia; 2006 Nov. 65. Joe LA, Jacobs RA, Guglielmo BJ. Systemic absorption of oral fluconazole after gastrointestinal resection. J Antimicrob Chemother. 1994; 33:1070. Letter. 66. Pelz RK, Lipsett PA, Swoboda SM et al. Enteral fluconazole is well absorbed in critically ill surgical patients. Surgery. 2002; 131:534-40. 67. Data on file for the gastrointestinal absorption of fluoxetine. Eli Lilly, Indianapolis; 2013 May. 68. Folic acid. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically.
CLINICAL CONSULTATION Medication absorption
69. Hepner GW, Booth CC, Cowan J et al. Absorption of crystalline folic acid in man. Lancet. 1968; 2:302-6. 70. Lee WI, Yoon WH, Shin WG et al. Pharmacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum. Biopharm Drug Dispos. 1997; 18:753-67. 71. Data on file for the gastrointestinal absorption of gabapentin. Pfizer, New York; 2005 Jul. 72. Rashid H, Long JD, Wadleigh RG. Management of secretions in esophageal cancer patients with glycopyrrolate. Ann Oncol. 1997; 8:198-9. 73. Griseofulvin. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 74. Kagan L, Lavy E, Hoffman A. Effect of mode of administration on guaifenesin pharmacokinetics and expectorant action in the rat model. Pulm Pharmacol Ther. 2009; 22:260-5. 75. Nakayama A, Eguchi O, Hatakeyama M et al. Different absorption behaviors among steroid hormones due to possible interaction with P-glycoprotein in the rat small intestine. Biol Pharm Bull. 1999; 22:535-8. 76. Data on file for the gastrointestinal absorption of hydromorphone. Abbott Pharmaceuticals, North Chicago, IL; 2007 Feb. 77. Data on file for the gastrointestinal absorption of hydroxychloroquine. Sanofiaventis, Bridgewater, NJ; 2007 Jan. 78. Data on file for the gastrointestinal absorption of isotretinoin. Mylan Pharmaceuticals, Canonsburg, PA; 2013 Aug. 79. Lactobacillus. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 80. Data on file for the gastrointestinal absorption of lamivudine. Viiv Pharmaceuticals, Brentford, United Kingdom; 2013 May. 81. Birnbaum AK, Kriel RL, Im Y et al. Relative bioavailability of lamotrigine chewable dispersible tablets administered rectally. Pharmacotherapy. 2001; 21:158-62. 82. Data on file for the gastrointestinal absorption of lansoprazole. Takeda, Deerfield, IL; 2013 Jun. 83. Stockis A, Sargentini-Maier ML, Otoul C et al. Assessment of levetiracetam bioavailability from targeted sites in the human intestine using remotely activated capsules and gamma scintigraphy: open-label, single-dose, randomized, four-way crossover study in healthy male volunteers. Clin Ther. 2010; 32:1813-21. 84. Levothyroxine. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 85. Reid J, Marciniuk D, Peloquin CA et al. Pharmacokinetics of antituberculosis medications delivered via percutaneous gastrojejunostomy tube. Chest. 121:281-4.
86. Data on file for the gastrointestinal absorption of linezolid. Pfizer, New York; 2007 Feb. 87. Data on file for the gastrointestinal absorption of loperamide. McNeil Consumer and Specialty Pharmaceuticals, Washington, PA; 2011 Dec. 88. Boffito M, Arnaudo I, Raiteri R et al. Clinical use of lopinavir/ritonavir in a salvage therapy setting: pharmacokinetics and pharmacodynamics. AIDS. 2002; 16:2081-3. 89. Kamimura M, Watanabe K, Kobayakawa M et al. Successful absorption of antiretroviral drugs after gastrojejunal bypass surgery following failure of therapy through a jejunal tube. Intern Med. 2009; 48:1103-4. 90. Data on file for the gastrointestinal absorption of lorazepam. Roxane, Columbus, OH; 2005 Apr. 91. Magnesium. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 92. Medium-chain triglyceride (MCT) oil. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 93. Data on file for the gastrointestinal absorption of MCT oil. Novartis Nutrition, St. Louis; 2008 Jan. 94. Data on file for the gastrointestinal absorption of mesalamine. Proctor & Gamble Pharmaceuticals, Cincinnati; 2013 May. 95. Vidon N, Chaussade S, Noel M et al. Metformin in the digestive tract. Diabetes Res Clin Pract. 1988; 4:223-9. 96. Data on file for the gastrointestinal absorption of methadone. Mallinckrodt, St. Louis; 2013 Jun. 97. Data on file for the gastrointestinal absorption of methylphenidate. Janssen Pharmaceuticals, Titusville, NJ; 2013 May. 98. Data on file for the gastrointestinal absorption of metoclopramide. Baxter, Deerfield, IL; 2013 May. 99. Data on file for the gastrointestinal absorption of metolazone. UCB Pharmaceuticals, Smyrna, GA; 2013 May. 100. Jobin G, Cortot A, Godbillon J et al. Investigation of drug absorption from the gastrointestinal tract of man. I. Metoprolol in the stomach, duodenum and jejunum. Br J Clin Pharmacol. 1985; 19(suppl 2):97S-105S. 101. Data on file for the gastrointestinal absorption of metronidazole. Pfizer, New York; 2013 May. 102. Data on file for the gastrointestinal absorption of mexiletine. Teva Pharmaceuticals, Tikva, Israel; 2013 May. 103. Jamei M, Yang J, Turner D et al. A novel physiologically-based mechanistic model for predicting oral drug absorption: the advanced dissolution, absorption, and metabolism (ADAM) model. Poster presented at the Fourth World Conference on Drug Absorption, Transport and Delivery. Kanazawa, Japan; 2007.
104. Okura T, Ozawa T, Ibe M et al. Effects of repeated morphine treatment on the antinociceptive effects, intestinal absorption, and efflux from intestinal epithelial cells of morphine. Biol Pharm Bull. 2009; 32:1571-5. 105. Bullingham R, Monroe S, Nicholls A et al. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clin Pharmacol. 1996; 36:315-24. 106. Data on file for the gastrointestinal absorption of nadolol. King Pharmaceuticals (Pfizer), Bristol, TN; 2013 May. 107. Neomycin. Lexicomp online. Hudson, OH: Wolters Kluwer Health; 2013. Updated periodically. 108. Data on file for the gastrointestinal absorption of nystatin. Taro Pharmaceuticals, Hawthorne, NY; 2013 Apr. 109. Data on file for the gastrointestinal absorption of olanzapine. Eli Lilly, Indianapolis; 2013 May. 110. Phillips JO, Olsen KM, Rebuck JA et al. A randomized, pharmacokinetic and pharmacodynamic, cross-over study of duodenal or jejunal administration compared to nasogastric administration of omeprazole suspension in patients at risk for stress ulcers. Am J Gastroenterol. 2001; 96:367-72. 111. Ariano RE, Sitar DS, Zelenitsky SA et al. Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza. CMAJ. 2010; 182:357-63. 112. Data on file for the gastrointestinal absorption of oxcarbazepine. Novartis, St. Louis; 2013 Jun. 113. Data on file for the gastrointestinal absorption of paroxetine. GlaxoSmithKline, Research Triangle Park, NC; 2013 Jun. 114. Data on file for the gastrointestinal absorption of pentobarbital. Lundbeck Pharmaceuticals, Deerfield, IL; 2013 May. 115. Tanaka C, Yagi H, Sakamoto M et al. Decreased phenobarbital absorption with charcoal administration for chronic renal failure. Ann Pharmacother. 2004; 38:73-6. 116. El-Darouti MA, El Nabarawy E, AbdelHalim MR et al. Phenytoin absorption in epidermolysis bullosa. Egypt J Dermatol Androl. 2009; 29:25-32. 117. Treiman DM, Woodbury DM. Phenytoin: absorption, distribution, and excretion. In: Levy RH, Mattson RH, Meldrum BS, eds. Antiepileptic drugs, 4th ed. New York: Raven; 1995:301-14. 118. Scharrer E. Phosphate absorption at different intestinal sites in the developing lamb. Q J Exp Physiol. 1985; 70:615-21. 119. Hurwitz S, Clarkson TW, Bar A. Intestinal absorption of sodium and potassium in the laying fowl. J Nutr. 1970; 100:1181-7. 120. Triscari J, Swanson BN, Willard DA et al. Steady state serum concentrations of pravastatin and digoxin when given in
Am J Health-Syst Pharm—Vol 71 Apr 1, 2014
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CLINICAL CONSULTATION Medication absorption
combination. Br J Clin Pharmacol. 1993; 36:263-5. 121. Bockbrader HN, Wesche D, Miller R et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010; 49:661-9. 122. Buch A, Barr WH. Absorption of propranolol in humans following oral, jejunal, and ileal administration. Pharm Res. 1998; 15:953-7. 123. Data on file for the gastrointestinal absorption of ramelteon. Takeda Pharmaceueticals, Deerfield, IL; 2008 Feb. 124. Levitt DG, Schoemaker RC. Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat. BMC Clin Pharmacol. 2006; 6:1. 125. Data on file for the gastrointestinal absorption of ranitidine. GlaxoWellcome, London, England; 2000 Mar. 126. Gramatte T, el Desoky E, Klotz U. Sitedependent small intestinal absorption of ranitidine. Eur J Clin Pharmacol. 1994; 46:253-9. 127. Williams MF, Dukes GE, Heizer W et al. Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine. Pharm Res. 1992; 9:1190-4. 128. Data on file for the gastrointestinal absorption of risperidone. Janssen Pharmaceuticals, Titusville, NJ; 2013 May. 129. Senna. In: McEvoy GK, ed. AHFS drug information 2013. Bethesda, MD: American Society of Health-System Pharmacists; 2013. 130. Data on file for the gastrointestinal absorption of sertraline. Pfizer, New York; 2003 Mar.
556
131. Data on file for the gastrointestinal absorption of sevelamer. Sanofi-Aventis, Bridgewater, NJ; 2013 Jan. 132. Data on file for the gastrointestinal absorption of sildenafil. Pfizer, New York; 2008 Dec. 133. Data on file for the gastrointestinal absorption of sirolimus. Wyeth Pharmaceuticals, Philadelphia; 2008 Dec. 134. Data on file for the gastrointestinal absorption of spironolactone. Searle, Skokie, IL; 2000 Nov. 135. Data on file for the gastrointestinal absorption of sucralfate. Aptalis Pharma, Bridgewater, NJ; 2013 Jun. 136. Data on file for the gastrointestinal absorption of tacrolimus. Astellas Pharmaceuticals, Northbrook, IL; 2013 May. 137. Kadono K, Yokoe J, Ogawara K et al. Analysis and prediction of absorption behavior for theophylline orally administered as powders based on gastrointestinal-transit-absorption (Gita) model. Drug Metab Pharmacokinet. 2002; 17:307-15. 138. Data on file for the gastrointestinal absorption of tizanidine. Acorda Therapeutics, Ardsley, NY; 2013 May. 139. Kayden HJ, Traber MG. Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res. 1993; 34:343-58. 140. Data on file for the gastrointestinal absorption of topiramate. Janssen Pharmaceuticals, Titusville, NJ; 2013 May. 141. Limited KHK: report on deliberation results for topiramate, in evaluation and licensing division PaFSB (ed). Tokyo, Japan: Takeda; 2007:22. 142. Ursodiol. Clinical Pharmacology [Internet database]. Tampa: Gold Standard; 2013. Updated periodically.
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143. Data on file for the gastrointestinal absorption of valproic acid. Abbvie, Chicago; 2013 May. 144. Data on file for the gastrointestinal absorption of vigabatrin. Lundbeck Pharmaceuticals, Deerfield, IL; 2011 Mar. 145. Abbot EL, Grenade DS, Kennedy DJ et al. Vigabatrin transport across the human intestinal epithelial (Caco-2) brushborder membrane is via the H+-coupled amino-acid transporter hPAT1. Br J Pharmacol. 2006; 147:298-306. 146. Data on file for the gastrointestinal absorption of voriconazole. Pfizer, New York; 2011 Dec. 147. Kearns PJ Jr, O’Reilly RA. Bioavailability of warfarin in a patient with severe short bowel syndrome. J Parenter Enteral Nutr. 1986; 10:100-1. 148. Lutomski DM, LaFrance RJ, Bower RH et al. Warfarin absorption after massive small bowel resection. Am J Gastroenterol. 1985; 80:99-102. 149. Data on file for the gastrointestinal absorption of zidovudine. GlaxoSmithKline, Research Triangle Park, NC; 2013 May. 150. Neve J, Hanocq M, Peretz A et al. Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation. Eur J Drug Metab Pharmacokinet. 1991; 16:315-23. 151. Data on file for the gastrointestinal absorption of zonisamide. Eisai, Woodcliff Lake, NJ; 2013 May. 152. Ashbrook M, Walenga JM, Schwartz J et al. Left ventricular assist device-induced coagulation and platelet activation and effect of the current anticoagulant therapy regimen. Clin Appl Thromb Hemost. 2013; 19:249-55.
