ANTIMICROBIAL AGENT8 AND CHEMOTHERAPY, Aug. 1977, p. 157-162 Copyright © 1977 American Society for Microbiology
Vol. 12, No. 2 Printed in U.S.A.
Comparative Pharmacology of Cefaclor and Cephalexin OKSANA M. KORZENIOWSKI, W. MICHAEL SCHELD, and MERLE A. SANDE* Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901
Received for publication 9 February 1977
Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 + 0.55 (standard deviation [SD]) ,ug/ml compared with 9.43 + 2.36 ,g/ml for cephalexin (P < 0.01). The half-lives were 0.58 + 0.07 (SD) h and 0.80 + 0.12 (SD) h, and elimination constants were 1.22 + 0.15 and 0.88 + 0.13 h-1 for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated. and their weights ranged between 145 and 220 pounds (ca. 72 to 110 kg). Prestudy physical examinations and laboratory parameters were normal. Procedure. The subjects were randomly divided into two groups of 10 individuals each. They were assigned to a crossover sequence of the two antibiotic regimens to be taken during two separate dosing periods. Each dosing period was 4 days in duration and separated by 1 week. Group I received 250 mg of cefaclor in capsules orally every 6 h (q6h) during the first period, followed by 250 mg of cephalexin in capsule form orally q6h during the second dosing period. Group II followed a reverse order. All subjects complied with the dosage time schedule. All subjects fasted for 8 h before each dosing period. After the first dose, a fast of 2 h was maintained before and after each subsequent dose. A control venous blood sample was drawn before the first dose and showed no detectable antibiotic activity in either of the two dosing periods. Venous blood samples for assay of plasma antibiotic concentration were obtained at 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 24.0, 36.0, 48.0, 60.0, 72.0, 72.5, 72.75, 73.0, 73.5, 74.0, 75.0, 76.0, 78.0, and 90.0 h after the initial dose. Urine samples were collected in 2-h intervals from time 0 to 6 h and from 72 to 78 h. There was a loss of up to 50% activity of cefaclor in serum samples that were left at room temperatures for 3 to 8 h. Therefore, all blood samples were immediately iced, and the serum was separated in a refrigerated centrifuge and either immediately placed in a - 70°C freezer or assayed. Using these precautions, a 14.17 + 1.47 (standard deviation [SD])% loss of activity was found in 16 samples evaluated. The following tests were performed before and MATERIALS AND METHODS after each dosing period: hemoglobin, hematocrit, Antibiotics. Cefaclor and cephalexin were sup- leukocyte count and differential, platelet estimation, urinalysis, blood urea nitrogen, glucose, soplied by Eli Lilly and Co., Indianapolis, Ind. Human volunteers. Twenty healthy men with no dium, potassium, chloride, bicarbonate, calcium, known allergies to cephalosporin antibiotics partici- phosphorus, alkaline phophatase, lactic dehydropated in the studies after informed written consent genase, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, cholesterol, was obtained. None were taking any other antimicrobial agents during the investigational period. total bilirubin, total protein, albumin, uric acid, and Their ages ranged between 21 and 32 years of age creatinine. Creatinine clearances were performed 157
Cefaclor, 3-chloro-7-n-(2-phenylglycinamido)3-cephem-4-carboxylic acid, is a new semisynthetic cephalosporin antibiotic derived from cephalexin. Preliminary reports indicate greater in vitro activity against strains susceptible to the parent compound, with the added advantage of greater bactericidal effect against ,8-lactamase-producing Haemophilus influen.zae (N. J. Bill and J. A. Washington, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 356, 1976; and D. A. Preston, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th. Chicago, Ill., Abstr. no. 342, 1976). In our laboratory, cefaclor was tested against 200 strains of gram-negative bacilli; 78% of the strains were inhibited by uz t qouM r co cn o co
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Vol. 12, No. 2 Printed in U.S.A.
Comparative Pharmacology of Cefaclor and Cephalexin OKSANA M. KORZENIOWSKI, W. MICHAEL SCHELD, and MERLE A. SANDE* Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22901
Received for publication 9 February 1977
Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 + 0.55 (standard deviation [SD]) ,ug/ml compared with 9.43 + 2.36 ,g/ml for cephalexin (P < 0.01). The half-lives were 0.58 + 0.07 (SD) h and 0.80 + 0.12 (SD) h, and elimination constants were 1.22 + 0.15 and 0.88 + 0.13 h-1 for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated. and their weights ranged between 145 and 220 pounds (ca. 72 to 110 kg). Prestudy physical examinations and laboratory parameters were normal. Procedure. The subjects were randomly divided into two groups of 10 individuals each. They were assigned to a crossover sequence of the two antibiotic regimens to be taken during two separate dosing periods. Each dosing period was 4 days in duration and separated by 1 week. Group I received 250 mg of cefaclor in capsules orally every 6 h (q6h) during the first period, followed by 250 mg of cephalexin in capsule form orally q6h during the second dosing period. Group II followed a reverse order. All subjects complied with the dosage time schedule. All subjects fasted for 8 h before each dosing period. After the first dose, a fast of 2 h was maintained before and after each subsequent dose. A control venous blood sample was drawn before the first dose and showed no detectable antibiotic activity in either of the two dosing periods. Venous blood samples for assay of plasma antibiotic concentration were obtained at 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 24.0, 36.0, 48.0, 60.0, 72.0, 72.5, 72.75, 73.0, 73.5, 74.0, 75.0, 76.0, 78.0, and 90.0 h after the initial dose. Urine samples were collected in 2-h intervals from time 0 to 6 h and from 72 to 78 h. There was a loss of up to 50% activity of cefaclor in serum samples that were left at room temperatures for 3 to 8 h. Therefore, all blood samples were immediately iced, and the serum was separated in a refrigerated centrifuge and either immediately placed in a - 70°C freezer or assayed. Using these precautions, a 14.17 + 1.47 (standard deviation [SD])% loss of activity was found in 16 samples evaluated. The following tests were performed before and MATERIALS AND METHODS after each dosing period: hemoglobin, hematocrit, Antibiotics. Cefaclor and cephalexin were sup- leukocyte count and differential, platelet estimation, urinalysis, blood urea nitrogen, glucose, soplied by Eli Lilly and Co., Indianapolis, Ind. Human volunteers. Twenty healthy men with no dium, potassium, chloride, bicarbonate, calcium, known allergies to cephalosporin antibiotics partici- phosphorus, alkaline phophatase, lactic dehydropated in the studies after informed written consent genase, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, cholesterol, was obtained. None were taking any other antimicrobial agents during the investigational period. total bilirubin, total protein, albumin, uric acid, and Their ages ranged between 21 and 32 years of age creatinine. Creatinine clearances were performed 157
Cefaclor, 3-chloro-7-n-(2-phenylglycinamido)3-cephem-4-carboxylic acid, is a new semisynthetic cephalosporin antibiotic derived from cephalexin. Preliminary reports indicate greater in vitro activity against strains susceptible to the parent compound, with the added advantage of greater bactericidal effect against ,8-lactamase-producing Haemophilus influen.zae (N. J. Bill and J. A. Washington, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th, Chicago, Ill., Abstr. no. 356, 1976; and D. A. Preston, Prog. Abstr. Intersci. Conf. Antimicrob. Agents Chemother. 16th. Chicago, Ill., Abstr. no. 342, 1976). In our laboratory, cefaclor was tested against 200 strains of gram-negative bacilli; 78% of the strains were inhibited by uz t qouM r co cn o co
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