Population Pharmacokinetic Modeling of Olmesartan, the Active Metabolite of Olmesartan Medoxomil, in Patients with Hypertension.

BACKGROUND: Olmesartan medoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension.

OBJECTIVE: The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartan medoxomil, in Indian hypertensive patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan.

METHODS: The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1.3 with a non-linear mixed-effect model. Bootstrap and visual predictive check were used simultaneously to validate the final population pharmacokinetic models. The covariates included age, sex, body surface area (BSA), bodyweight, height, creatinine clearance (CLCR ) as an index of renal function and liver parameters as indices of hepatic function.

RESULTS: A total of 205 olmesartan plasma sample concentrations from 69 patients with hypertension were collected in this study. The pharmacokinetic data of olmesartan was well described by a two-compartment linear pharmacokinetic model with first-order absorption and an absorption lag-time. The mean values of CL/F and V/F of olmesartan in the patients were 0.31565 L/h and 44.5162 L, respectively. Analysis of covariates showed that age and CLCR were factors influencing the clearance of olmesartan and the volume of distribution of olmesartan was dependent on age and BSA.

CONCLUSION: The final population pharmacokinetic model was demonstrated to be appropriate and effective and it can be used to assess the pharmacokinetic parameters of olmesartan in Indian patients with hypertension.