Assessment of Ethnic Differences in the Pharmacokinetics and Pharmacodynamics of Valsartan

Objective: To assess the potential ethnic differences in pharmacokinetics and pharmacodynamics of valsartan between Japanese and Caucasian subjects. Methods: This was an open-label, parallel-design study conducted in male Japanese (n=15) and Caucasian (n=15) subjects with similar age and body weight. All subjects received a single oral dose of 160 mg valsartan capsule, and the plasma levels of valsartan, aldosterone, and angiotensin II along with plasma renin activity (PRA) were determined at pre-set time intervals, post-dosing. Key findings: The time to reach peak plasma concentrations of valsartan (T max ) was in the range of 1–6 h in both groups. The mean C max of valsartan was 3.3 and 3.6 μg/ml; the mean plasma exposure (AUC 0- ∞ ) values were 23.0 and 23.8 μg.h/ml and the mean half-life (t 1/2 ) was 7.7 and 9.6 h in Japanese and Caucasian subjects, respectively. No significant difference (p>0.1) was found between two ethnic groups for PRA, angiotensin II and aldosterone at 2, 4 and 8 h, post dose. Conclusion: Pharmacokinetics and pharmacodynamics of valsartan were not found to be associated with ethnic differences between healthy male Caucasian and Japanese subjects following single oral dose administration of valsartan and hence no dose adjustment is required for these groups.