Comparative Pharmacology of Cefaclor and Cephalexin

Abstract

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. 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 after each dosing period: hemoglobin, hematocrit, leukocyte count and differential, platelet estimation, urinalysis, blood urea nitrogen, glucose, sodium, potassium, chloride, bicarbonate, calcium, phosphorus, alkaline phophatase, lactic dehydrogenase, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, cholesterol, total bilirubin, total protein, albumin, uric acid, and creatinine. Creatinine clearances were performed 157 on May 9, 2018 by guest http://aac.asm.org/ Downloaded from

Pharmacokinetics of Cefaclor and Cephalexin: Dosage Nomograms for Impaired Renal Function

“…This means that, at a CorCcr of 100 ml/min, 29% of cefaclor was probably being excreted by a nonrenal route, compared with only 6% for cephalexin. This is in close agreement with the 62% urinary recovery in this study and our previous study in which we found 70% urinary recovery for cefaclor and 96% recovery for cephalexin (7). In any event, the half-life of cefaclor of 2 to 3 h for a CorCcr of 0 suggests that drug accumulation will be negligible even for a 6-h dosage regimen in anephric patients.…”

“…The metabolism of cefaclor has been examined in three species of laboratory animals (13) and in normal volunteers (7). Cefaclor is chemically similar to other cephalosporins recently reviewed by Nightingale et al (8).…”

“…Samples were stored in duplicate and frozen at -50°C until assayed. The cephalosporin concentration of the sera was determined by an agar well diffusion technique, using Bacillus subtilis as previously described (7). The sensitivity of this assay is 0.3 Atg/ml, and complete standard curves were prepared for each assay by using human serum.…”

“…It differs from cephalexin only in the substitution of a chlorine for the methyl group in the 3' position, but exhibits improved antibacterial activity against Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, and most enteric pathogens (9); Cefaclor appears to be well absorbed orally in humans; after a 250-mg oral dosage, cefaclor -achieves serum levels approximately one-half those of cephalexin (7).…”

Concentration Relationships of Cefaclor in Serum, Interstitial Fluid, Bile, and Urine of Dogs

“…Although its in vitro activity against Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis is similar in range to those of other oral cephalosporins, cefaclor has been shown to be signiflcantly more active at lower and more easily attainable concentrations against the cephalosporin-susceptible Enterobacteriaceae as well as staphylococci, streptococci, and gonococci (2, 9-11). The antibiotic is excreted in high concentrations in the urine of humans and experimental animals (7,12).…”