Letter to Editor
as a basic over the counter drug in many countries. Nevertheless, the concern of its dependence is not well recognized by the general practitioners.[2,3] Since this drug is widely sold and easily available in some settings, the patients usually have this drug as a simple drug for relieving of their diarrheal symptoms. The consideration is the frequent use of this drug can result in dependence and this will bring difficulty in management of the gastrointestinal disorder. In addition, the illegal use of this drug as narcotic and further preparation as other more potent narcotics might be expected. In Thailand, this drug is widely sold, but there has never been any report on the dependence. However, the intoxication of this drug due to excessive ingestion has been reported.[4] The common presentations of overdose intoxication include “central nervous system excitement, hypertension, fever, and flushed dry skin.”[5] As Mehra et al. noted, it should be the time to consider the restriction and control of lomotil usage.
Address for correspondence: Dr. Beuy Joob, Sanitation 1 Medical Academic Center, Bangkok, Thailand. E-mail: [email protected]
REFERENCES 1. Mehra A, Sarkar S, Basu D. Lomotil (diphenoxylate) dependence in India. Indian J Psychol Med 2013;35:248-50. 2. Rao R, Agrawal A, Pal HR, Mohan I. Lomotil dependence: A note of caution. Natl Med J India 2005;18:330-1. 3. Firoozabadi A, Mowla A, Farashbandi H, Gorman JM. Diphenoxylate hydrochloride dependency. J Psychiatr Pract 2007;13:278-80. 4. Thasniyom S. Lomotil intoxication. Khonkaen Hosp Med J 1976;1:56-61. 5. M c C a r r o n M M , C h a l l o n e r K R , T h o m p s o n G A . Diphenoxylate-atropine (Lomotil) overdose in children: An update (report of eight cases and review of the literature). Pediatrics 1991;87:694-700. Access this article online Quick Response Code Website:
Beuy Joob, Viroj Wiwanitkit Department of Sanitation 1 Medical Academic Center, Bangkok, Thailand, 1Hainan Medical University, China, University of Nis, Serbia, and Joseph Ayobabalola University, Nigeria
www.ijpm.info
DOI: 10.4103/0253-7176.135401
Time Matters!: When is the Right Time to Estimate Serum Valproic Acid Levels? Sir, Divalproex sodium extended release (ER) preparations received Food and Drug Administration approval as monotherapy for management of acute mania in 2005.[1] It is intended for once daily (OD) oral administration and maintains a steady state plasma concentration for 24 h.[2] The therapeutic range is maintained through controlling its release. Therapeutic efficacy is associated with a trough level concentration between 50 and 100 mmol/L (trough levels). Though it does not have a narrow therapeutic range as in the case of lithium, accurate estimation of its trough level is essential as any value below the lower limit of the therapeutic range is not effective and above it may result in adverse effects.[3] Trough levels are more accurate when measured just before the next dose. After a once-daily divalproex-ER dose, the timing of the blood sample does matter and Indian Journal of Psychological Medicine | Jul - Sep 2014 | Vol 36 | Issue 3
impacts the proper interpretation of the valproic acid (VPA) concentration. There is no one consensus that we depend upon for an optimal time to estimate the trough levels, which impacts the proper interpretation of the VPA concentration. In general, when taking divalproexER once daily in the morning, a blood sample collected at 21-24 h after OD dose of ER preparation is expected to have a concentration within 3% of the trough value. Conversely, blood sample 12-15 h after the last dosing will give a value that is 18-25% higher, than the actual trough value.[2] The current study is undertaken with an aim to provide with an appropriate time for serum VPA level estimation (for trough levels) after a single dose of divalproex sodium ER. This cross-sectional study involves analyzing serum VPA levels in patients with bipolar disorder compliant with ER preparations of divalproex sodium. The dose 349
Letter to Editor
was administered at 8 pm and blood samples were collected at 12 and 24 h after the last dose (medication is obtained from a single manufacturer and analysis was done in a single lab). The results were analyzed using standard statistical techniques. Mean and standard deviation [Table 1] was calculated for the serum VPA levels at 12 h and at 24 h. Serum VPA levels after 12 h (µ = 88.9, σ = 26.8) was 1.3 times higher than the 24 h levels (µ = 66, σ = 22.1) after an OD dose [Figure 1].
OD dosing would give a 1.3 times higher value than the actual trough value. Trough sampling is easily achieved just before a morning daily dose, but the issue arises when patient receives a night dose, because collecting a blood sample 21-24 h later may be limited by the operational hours of laboratory. To avoid patients’ inconvenience, serum VPA levels can be tested at 12 h though have to be reduced by 1.3 times to calculate the accurate trough levels.
Swetha Reddy Damegunta
It is observed that measuring serum VPA levels at 24 h is recommended and provides a more accurate value for patients on OD dosage. Measuring it at 12 h in case of Table 1: Serum VPA levels at 12 h and 24 h post an OD dose of extended release preparation of divalproex sodium Variable n Dosage: Mean (SD) Serum levels: mean (SD) Range at 95% CI
Result 27 990 (189.6) At 12 h (mmol/L) 88.79 (26.76) 93.94-83.63
At 24 h (mmol/L) 65.95 (22.18) 70.22-61.67
VPA – Valproic acid; OD – Once a day, SD – Standard deviation, CI – Confidence interval 160 140
12 hours 24 hours
120 100
Department of Psychiatry, Asha Bipolar Clinic, Asha Hospital, Hyderabad, Andhra Pradesh, India Address for correspondence: Dr. Swetha Reddy Damegunta, Department of Psychiatry, Asha Bipolar Clinic, Asha Hospital, Hyderabad, Andhra Pradesh, India. E-mail: [email protected]
REFERENCES 1. Centorrino F, Kelleher JP, Berry JM, Salvatore P, Eakin M, Fogarty KV, et al. Pilot comparison of extended-release and standard preparations of divalproex sodium in patients with bipolar and schizoaffective disorders. Am J Psychiatry 2003;160:1348-50. 2. Reed RC, Dutta S. Does it really matter when a blood sample for valproic acid concentration is taken following oncedaily administration of divalproex-ER? Ther Drug Monit 2006;28:413-8. 3. Ghaemi SN. Mood Disorders; A Practical Guide. 2nd ed. New Delhi, Philadelphia: Lippincott Williams and Wilkins, Wolters Kluwer Pvt. Ltd.; 2009.
80
Access this article online
60
Quick Response Code
40
Website:
20
www.ijpm.info 1000 1000 1000 1000 1000 1000 1000 750 1000 1000 1000 1500 1000 1000 500 1000 750 1000 1000 1000 1000 1500 1000 1000 1000 1000 750
0
Figure 1: Chart depicting the individual subject’s serum valproic acid levels at 12 and 24 h
350
DOI: 10.4103/0253-7176.135402
Indian Journal of Psychological Medicine | Jul - Sep 2014 | Vol 36 | Issue 3
Copyright of Indian Journal of Psychological Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
as a basic over the counter drug in many countries. Nevertheless, the concern of its dependence is not well recognized by the general practitioners.[2,3] Since this drug is widely sold and easily available in some settings, the patients usually have this drug as a simple drug for relieving of their diarrheal symptoms. The consideration is the frequent use of this drug can result in dependence and this will bring difficulty in management of the gastrointestinal disorder. In addition, the illegal use of this drug as narcotic and further preparation as other more potent narcotics might be expected. In Thailand, this drug is widely sold, but there has never been any report on the dependence. However, the intoxication of this drug due to excessive ingestion has been reported.[4] The common presentations of overdose intoxication include “central nervous system excitement, hypertension, fever, and flushed dry skin.”[5] As Mehra et al. noted, it should be the time to consider the restriction and control of lomotil usage.
Address for correspondence: Dr. Beuy Joob, Sanitation 1 Medical Academic Center, Bangkok, Thailand. E-mail: [email protected]
REFERENCES 1. Mehra A, Sarkar S, Basu D. Lomotil (diphenoxylate) dependence in India. Indian J Psychol Med 2013;35:248-50. 2. Rao R, Agrawal A, Pal HR, Mohan I. Lomotil dependence: A note of caution. Natl Med J India 2005;18:330-1. 3. Firoozabadi A, Mowla A, Farashbandi H, Gorman JM. Diphenoxylate hydrochloride dependency. J Psychiatr Pract 2007;13:278-80. 4. Thasniyom S. Lomotil intoxication. Khonkaen Hosp Med J 1976;1:56-61. 5. M c C a r r o n M M , C h a l l o n e r K R , T h o m p s o n G A . Diphenoxylate-atropine (Lomotil) overdose in children: An update (report of eight cases and review of the literature). Pediatrics 1991;87:694-700. Access this article online Quick Response Code Website:
Beuy Joob, Viroj Wiwanitkit Department of Sanitation 1 Medical Academic Center, Bangkok, Thailand, 1Hainan Medical University, China, University of Nis, Serbia, and Joseph Ayobabalola University, Nigeria
www.ijpm.info
DOI: 10.4103/0253-7176.135401
Time Matters!: When is the Right Time to Estimate Serum Valproic Acid Levels? Sir, Divalproex sodium extended release (ER) preparations received Food and Drug Administration approval as monotherapy for management of acute mania in 2005.[1] It is intended for once daily (OD) oral administration and maintains a steady state plasma concentration for 24 h.[2] The therapeutic range is maintained through controlling its release. Therapeutic efficacy is associated with a trough level concentration between 50 and 100 mmol/L (trough levels). Though it does not have a narrow therapeutic range as in the case of lithium, accurate estimation of its trough level is essential as any value below the lower limit of the therapeutic range is not effective and above it may result in adverse effects.[3] Trough levels are more accurate when measured just before the next dose. After a once-daily divalproex-ER dose, the timing of the blood sample does matter and Indian Journal of Psychological Medicine | Jul - Sep 2014 | Vol 36 | Issue 3
impacts the proper interpretation of the valproic acid (VPA) concentration. There is no one consensus that we depend upon for an optimal time to estimate the trough levels, which impacts the proper interpretation of the VPA concentration. In general, when taking divalproexER once daily in the morning, a blood sample collected at 21-24 h after OD dose of ER preparation is expected to have a concentration within 3% of the trough value. Conversely, blood sample 12-15 h after the last dosing will give a value that is 18-25% higher, than the actual trough value.[2] The current study is undertaken with an aim to provide with an appropriate time for serum VPA level estimation (for trough levels) after a single dose of divalproex sodium ER. This cross-sectional study involves analyzing serum VPA levels in patients with bipolar disorder compliant with ER preparations of divalproex sodium. The dose 349
Letter to Editor
was administered at 8 pm and blood samples were collected at 12 and 24 h after the last dose (medication is obtained from a single manufacturer and analysis was done in a single lab). The results were analyzed using standard statistical techniques. Mean and standard deviation [Table 1] was calculated for the serum VPA levels at 12 h and at 24 h. Serum VPA levels after 12 h (µ = 88.9, σ = 26.8) was 1.3 times higher than the 24 h levels (µ = 66, σ = 22.1) after an OD dose [Figure 1].
OD dosing would give a 1.3 times higher value than the actual trough value. Trough sampling is easily achieved just before a morning daily dose, but the issue arises when patient receives a night dose, because collecting a blood sample 21-24 h later may be limited by the operational hours of laboratory. To avoid patients’ inconvenience, serum VPA levels can be tested at 12 h though have to be reduced by 1.3 times to calculate the accurate trough levels.
Swetha Reddy Damegunta
It is observed that measuring serum VPA levels at 24 h is recommended and provides a more accurate value for patients on OD dosage. Measuring it at 12 h in case of Table 1: Serum VPA levels at 12 h and 24 h post an OD dose of extended release preparation of divalproex sodium Variable n Dosage: Mean (SD) Serum levels: mean (SD) Range at 95% CI
Result 27 990 (189.6) At 12 h (mmol/L) 88.79 (26.76) 93.94-83.63
At 24 h (mmol/L) 65.95 (22.18) 70.22-61.67
VPA – Valproic acid; OD – Once a day, SD – Standard deviation, CI – Confidence interval 160 140
12 hours 24 hours
120 100
Department of Psychiatry, Asha Bipolar Clinic, Asha Hospital, Hyderabad, Andhra Pradesh, India Address for correspondence: Dr. Swetha Reddy Damegunta, Department of Psychiatry, Asha Bipolar Clinic, Asha Hospital, Hyderabad, Andhra Pradesh, India. E-mail: [email protected]
REFERENCES 1. Centorrino F, Kelleher JP, Berry JM, Salvatore P, Eakin M, Fogarty KV, et al. Pilot comparison of extended-release and standard preparations of divalproex sodium in patients with bipolar and schizoaffective disorders. Am J Psychiatry 2003;160:1348-50. 2. Reed RC, Dutta S. Does it really matter when a blood sample for valproic acid concentration is taken following oncedaily administration of divalproex-ER? Ther Drug Monit 2006;28:413-8. 3. Ghaemi SN. Mood Disorders; A Practical Guide. 2nd ed. New Delhi, Philadelphia: Lippincott Williams and Wilkins, Wolters Kluwer Pvt. Ltd.; 2009.
80
Access this article online
60
Quick Response Code
40
Website:
20
www.ijpm.info 1000 1000 1000 1000 1000 1000 1000 750 1000 1000 1000 1500 1000 1000 500 1000 750 1000 1000 1000 1000 1500 1000 1000 1000 1000 750
0
Figure 1: Chart depicting the individual subject’s serum valproic acid levels at 12 and 24 h
350
DOI: 10.4103/0253-7176.135402
Indian Journal of Psychological Medicine | Jul - Sep 2014 | Vol 36 | Issue 3
Copyright of Indian Journal of Psychological Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
