Effects of age and gender on pharmacokinetics of cefepime

Abstract

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 (t( 1/2 )) and weight-normalized total body clearance (CL(T)), renal clearance (CL(R)), and steady-state volume of distribution (V(ss)). Statistically significant age-related effects were found for t( 1/2 ), CL(T), CL(R), and V(ss) parameters. In different study groups, V(ss) ranged from 0.21 to 0.24 liter/kg. The values for V(ss) were significant greater for elderly subjects than they were for young subjects. The cefepime t( 1/2 ) was significantly longer in elderly subjects (about 3 h) than that observed in young subjects (about 2.2 h). The mean values for CL(T) and CL(R) 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 CL(T) and CL(R) 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.