A pharmacokinetic comparison of cefadroxil and cephalexin after administration of 250, 500 and 1000 mg solution doses.
The pharmacokinetics of cefadroxil and cephalexin were examined following single oral doses of either 250, 500 or 1000 mg to a total of 36 healthy volunteers. The volunteers were divided into groups of 12 per dose-group and solution doses of cefadroxil or cephalexin were administered after an overnight fast according to a crossover design for the cephalosporins but not for doses. Serial blood and urine samples were collected from each individual and were analyzed for cefadroxil or cephalexin using validated HPLC assays with UV detection. The individual subject plasma concentration-time data for each cephalosporin were analyzed using noncompartmental methods. Profiles for cephalexin in plasma showed sharper and higher peaks than those for cefadroxil. Although values for the peak concentrations (Cmax) for cefadroxil were lower than that of cephalexin, the levels of cefadroxil in plasma and urine remained above the reported minimum inhibitory concentrations of susceptible organisms for longer period of time than those of cefalexin. The elimination half-life (t1/2) of cefadroxil (about 2 h) was significantly longer than that of cephalexin (about 1 h). The values for Cmax and AUC0-infinity values for both these cephalosporins showed dose-proportional increase, whereas t1/2, renal clearance (CLR) remained independent of dose. These observations confirm that cefadroxil and cephalexin obey linear pharmacokinetics. The CLr of both the cephalosporins were significantly higher than the average glomerular filtration rate at each dose level. The urinary recovery (% Xu) of each cephalosporin, accounted for over 80 per cent of the administered dose, and no significant differences in % Xu were observed between the two cephalosporins. These data suggest that the systemic availability of cefadroxil and cephalexin is similar at each dose level.
Barbhaiya
R H
RH
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
D000328:Adult; D002434:Cefadroxil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002506:Cephalexin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D008297:Male; D012044:Regression Analysis; D012996:Solutions
D002511:Cephalosporins; D012996:Solutions; D002434:Cefadroxil; D002506:Cephalexin