Pharmacological Evaluation of Cefaclor in Volunteers

Shukla

et al. 1990

The objectives of this study were to assess the safety and tolerance of cefprozil, to characterize the pharmacokinetics of cefprozil after adiinistration of multiple doses of the drug, and to compare these pharmacokinetic parameters with those obtained with cefaclor. The volunteers received 28 doses of 250, 500, or 1,000 mg of cefprozil or 500 mg of cefaclor every 8 h for 10 days. Serial blood samples and the total volume of urine voided by each individual were collected for pharmacokinetic evaluation on days 1, 5, and 10. Both cephalosporins were well tolerated after multiple oral dosing. The greater than that of cefaclor. The half-life of cefprozil was also twofold longer than that observed for cefaclor. Although the urinary recovery of cefaclor (75% of dose) was significantly higher than that of cefprozil (61% of dose), the concentrations of cefprozil in urine remained significantly higher than those of cefaclor from 2 to 8 h postdosing. If the therapeutic concept is maintained that levels of beta-lactam antibiotics in plasma should exceed the MIC for the offending organisms over a period that approximates the dosing interval, then cefprozil would appear to be suitable for twice-daily administration, whereas cefaclor should probably be administered three or even four times a day.

Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Phase I study of multiple-dose cefprozil and comparison with cefaclor

Shukla

et al. 1990

“…Profiles of BMY-28100 levels in plasma show somewhat lower peak levels than those reported for cefaclor (5,7). The Cmax and Tmax data indicate that the absorption of BMY-28100 is slower than that of cefaclor.…”

Section: Methodsmentioning

confidence: 63%

“…The CLR averaged between 183 ml/min for the 1,000-mg dose and 212 ml/min for the 500-mg dose; no significant differences in mean (7,9), BMY-28100 is excreted by glomerular filtration and tubular secretion. In this respect, the pharmacokinetics of BMY-28100 are typical of other oral cephalosporins (5,7,9).…”

Section: Methodsmentioning

confidence: 99%

Phase I study of single-dose BMY-28100, a new oral cephalosporin

Shyu

et al. 1990

The objective of this Phase I study was to evaluate the safety, tolerance, and pharmacokinetics of BMY-28100 in 36 male subjects after the administration of single oral doses of 250, 500, and 1,000 mg. The subjects were divided into groups of 12 per dose group. All subjects completed the study, and BMY-28100 was well tolerated at all doses. The maximum concentration of the drug in plasma ranged from 6.2 to 17.7 Ig/mL for the 250-and 1,000-mg doses, respectively, and the area under the curve increased in a dose-proportional manner. The elimination half-life and renal clearance averages were 1.2 h and 200 ml/min, respectively. The values for renal clearance suggest that BMY-28100 is excreted by glomerular filtration and tubular secretion. Mean concentrations of the drug in urine were highest during the first 4 h after the doses and ranged from 175 to 658 .g/ml following the 250-and 1,000-mg doses, respectively. The mean urinary recovery ranged from 57 to 70% of the dose. The results from this Phase I study indicate that BMY-28100 is well tolerated and exhibits linear pharmacokinetics.

“…Several studies have defined the pharmacokinetics of cefprozil (1-3) and cefaclor (10,12,16,17) under fasting conditions. The results from the present study on the pharmacokinetic parameters of these cephalosporins under fasting conditions are in close agreement with previously published data.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the effects of food on the pharmacokinetics of cefprozil and cefaclor

Shukla

et al. 1990

The objective of this study was to assess the effects of food on the pharmacokinetics of cefprozil and cefaclor. A group of 12 healthy male volunteers received a single 250-mg dose of cefprozil or cefaclor under fasting conditions as well as after the intake of food. There was a 1-week washout period between each treatment. Serial blood samples were collected and assayed for cefprozil or cefaclor by specific high-pressure liquid chromatographic methods. The mean ± standard deviation peak concentration (Cm,.) of cefprozil in plasma was 6.13 ± 1.22 ,g/ml under the fasting condition and 5.27 ± 1.06 ,g/ml after breakfast, and these values were not significantly different from each other. The corresponding median time to reach Cm,. was prolonged after food intake, but this difference was not significant. The mean Cm. values of cefaclor decreased significantly from 8.70 ± 2.72 ,ug/ml under the fasting condition to 4.29 ± 1.52 ,ug/ml after breakfast, and the corresponding median times to reach Cm,., were significantly prolonged. The mean half-lives of cefprozil and cefaclor were nearly identical for the two treatments, suggesting that the elimination kinetics of these cephalosporins remained unaltered when the drugs were administered with food. The area under the plasma-concentration-versus-time curves for fasted and fed conditions were not significantly different for both drugs. The results of this study indicate that the extent of absorption and rate of elimination of both cephalosporins remain unaltered in the presence of food. However, the absorption rate of cefaclor is significantly reduced in the presence of food, while that of cefprozil remains unaltered. As a result, the C..,, of cefaclor is significantly reduced in the presence of food, whereas that of cefprozil is not significantly affected. Cefprozil can be administered with a meal without markedly affecting levels in blood.