Pharmacokinetic comparison of an angiotensin II receptor antagonist, telmisartan, in Japanese and western hypertensive patients using population pharmacokinetic method.

The objectives of this study were to develop a population pharmacokinetic (PPK) model for telmisartan based on the pooled data obtained from the different racial populations and then to identify the factors that affect the pharmacokinetics of telmisartan for the comparison between the regions. A PPK model was established based on the data of 1343 subjects in 12 clinical trials. The PK profiles of telmisartan were described with a 2-compartment model with first-order absorption. The obtained model could predict the observed plasma concentrations well. This PPK model suggested that CL/F was a function of age, dose, gender, race, alcohol consumption and liver function. A marked difference was observed in the plasma concentration profiles between Japanese and other countries' subjects. However, the effect of the factor "race" on CL/F was not large. In the present PPK model, "trial condition" affected all PK parameters except for V(2)/F. The condition differences were in food condition and formulation (Japanese: fed, capsule, US and EU: fasted, tablet). The extent of difference in the plasma concentration profiles simulated for Japanese and Caucasian using the PPK model under the same demographic condition was comparable with the results of the food effect study performed previously in Japan. The findings suggest that the difference in the plasma concentration profiles between Japanese and other countries' subjects was mainly due to the difference of food intake conditions under which the clinical trials were performed.