Population Pharmacokinetics of Eplerenone in Japanese Patients With Chronic Heart Failure.

To characterize eplerenone pharmacokinetics (PK) in Japanese chronic heart failure (CHF) patients and to estimate the impact of factors that may affect eplerenone PK, population pharmacokinetic (PPK) analysis was conducted. In addition, PK of Japanese CHF and Western CHF patients from a previous clinical pharmacology study were compared in the analysis. Eplerenone PK was characterized by a 1-compartment PPK model with first-order absorption and lag time in Japanese CHF patients. The population mean of apparent oral clearance (CL/F) in Japanese CHF patients was estimated as 5.31 L/h, which was similar to the mean CL/F for Western CHF patients. In the full model approach, creatinine clearance (CLcr) on CL/F and body weight on apparent central volume of distribution (Vc/F) were selected as factors that may affect PK. The effect of CLcr on CL/F predicted that CL/F would be decreased by 25% when CLcr was decreased from 80 mL/min to 50 mL/min. The effect of body weight on Vc/F predicted that Vc/F would be decreased by 18% when body weight was decreased from 80 kg to 60 kg. Distribution of individual CL/F estimates for Japanese CHF patients overlapped CL/F observed values for Western CHF patients, and CL/F values for Western CHF patients were contained within the distribution of CL/F estimates for Japanese CHF patients. No obvious difference between Japanese and Western subjects was detected even in the updated model by adding the data obtained from Western CHF patients and Western healthy adults to the model constructed with data from Japanese CHF patients.