Population pharmacokinetic analysis was conducted on
cefditoren pivoxil (
CDTR-PI), a third generation oral
antibiotic to evaluate the effect of covariates on pharmacokinetic parameters. Plasma concentrations of
cefditoren (CDTR, total number of sampling points: 2864) obtained from healthy adult subjects, elderlies, and subjects with renal dysfunction (287 subjects) after
CDTR-PI administration as well as demographic data of those subjects were used for analysis. We conducted the population pharmacokinetic analysis of
CDTR-PI using a nonlinear mixed effects modeling (NONMEM) method. A one-compartment model with a first-order absorption and lag time fitted well to plasma concentration-time curve for CDTR. The subject covariate significantly affecting pharmacokinetic parameters of
CDTR-PI was demonstrated by population pharmacokinetic analysis. The absorption rate constant (ka: hr(-1)) of
CDTR-PI decreased with age, total clearance adjusted by bioavailability (CL/F: L/hr/kg) increased with increasing
creatinine clearance adjusted by
body weight (Ccr: mL/min/kg) and volume of distribution adjusted by bioavailability (Vd/F: L/kg) decreased with increasing
body weight (WT: kg). In addition, the lag time (Tlag: hr) depends on formulation (
tablet or granule) of
CDTR-PI and the absorption lag time of the
tablet was longer than that of the granule. We could obtain the population mean parameters of
CDTR-PI together with interindividual variability and intraindividual residual variability after
oral administration of
CDTR-PI to adult subjects. In the future, this information will enable us to simulate the plasma concentrations of CDTR in subjects with various demographic backgrounds, which contributes to future examination of the efficacy and safety of
CDTR-PI.