The effects of age and gender on the pharmacokinetics of cefepime were examined in 48 volunteers following administration of a single 1,000-mg intravenous dose. Male and female subjects were divided into four groups, each consisting of 12 subjects, according to their age and gender. The young subjects were between 20 and 40 years of age and elderly subjects were between 65 and 81 years of age. Serial blood and urine samples were collected from each subject and were analyzed for cefepime by validated high-pressure liquid chromatographic assays with UV detection. Key pharmacokinetic parameters were calculated by noncompartmental methods.There were no gender-related differences in elimination half-life (tl2) and weight-normalized total body clearance (CLT), renal clearance (CLR), and steady-state volume of distribution (Vr,). Statistically significant age-related effects were found for t4/2, CLT, CLR, and V., parameters. In different study groups, Vr,, ranged from 0.21 to 0.24 liter/kg. The values for V., were significant greater for elderly subjects than they were for young subjects. The cefepime t112 was significantly longer in elderly subjects (about 3 h) than that observed in young subjects (about 2.2 h). The mean values for CLr and CLR in the four study groups ranged from 1.11 to 1.56 and 0.99 to 1.44 ml/min/kg, respectively. In elderly subjects, the estimates for CLr and CLR were significantly lower than those observed in young subjects. Linear regression revealed good correlations between clearance values of cefepime and creatinine. The magnitude of age-related changes in the pharmacokinetics of cefepime is not significant enough to recommend dosage adjustment in elderly patients with kidney functions normal for their age.Cefepime (BMY-28142) is a new parenteral "fourth-generation" cephalosporin antibiotic with a spectrum of antimicrobial activity broader than those of other new cephalosporins and nontraditional antibiotics (12, 18). The in vitro activities of cefepime have been reproduced in numerous in vivo infection models (19,28). Compared with cefotaxime, cefepime has been shown to be five-to ninefold more active against Pseudomonas aenrginosa (18). In addition, cefepime has been found to be approximately fourfold more active than ceftazidime against gram-positive organisms (12,18). Cefepime was also more active than ceftazidime, moxalactam, cefoperazone, cefpirome, and cefotaxime when the compounds were tested against 326 species of members of the family Enterobacteriaceae (18). Cefepime has a low affinity for major chromosomally mediated 1-lactamases (24).Values of key pharmacokinetic parameters after the administration of single and repeated intravenous and intramuscular doses to normal volunteers indicate that cefepime is safe and well-tolerated and exhibits linear pharmacokinetics within the 62.5-to 2,000-mg dose range (2, 3, 7).In normal subjects, cefepime is cleared primarily by urinary excretion in the unchanged form (2,3,6,7). Previous clinical studies with other cephalosporins indicate that th...