Population pharmacokinetics of faropenem in healthy human volunteers and patients

Faropenem (FRPM) is an oral penem antibacterial medicine with a high stability to beta-lactamase which has a broad antibacterial spectrum and a strong antibacterial activity to gram positive bacteria, and gram negative bacteria, except for Pseudomonas aeruginosa and anaerobic bacteria. The sale of faropene was started in 1997.Based on the plasma faropenem concentration vs. time data obtained from clinical trials using healthy adult volunteers and patients, and a post-marketing clinical study using advanced age patients, the population pharmacokinetic analysis of a total of 20 studies was performed. The concentration data of 1, 065 points from 218 patients whose creatinine clearances were measured (85 points/12 patients) or estimated (980 points/206 patients) from plasma concentration levels was used for the analysis.A one-compartment model with first-order absorption was used as a pharmacokinetic model where the absorption lag-time was assumed. Among the population pharmacokinetic parameters, the apparent total body clearance (CL), apparent distribution volume (V), first-order absorption rate constant (ka) and absorption lag-time (tiag) showed great inter-subject variation.In the final model, creatinine clearance (CLcr) was chosen as the most influential covariate against CL and CL was well correlated with CLcr when CLcr was less than 80 mL/min. The inter-subject variability in CL was explained by considering CLcr as a cofactor . The apparent distribution volume increased in the geriatric patients. Both ka and tiag were dependent on meals in all patients. Based on these results, the population pharmacokinetic model of faropenem was made by taking these covariates into consideration.From the results of population pharmacokinetics analysis. the prolongntion of the eliminntion half-lifp (t1/2) of faropenem was suggested in the patients with decreased kidney function as previously reported.