Pharmacokinetics and Safety of a Single Dose and Multiple Doses of Allisartan Isoproxil, an Angiotensin II Receptor Blocker, in Healthy Chinese People

Allisartan isoproxil (AI) is a blocker of the angiotensin II type 1 receptor. We evaluated the safety and pharmacokinetics of single- and multiple-dose AI in healthy Chinese individuals. Participants were assigned to receive AI or placebo. Plasma concentration of EXP3174 (carboxylic acid derivative) was measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental methods. Twelve subjects were enrolled, and the ratio of men to women was 5:1. Main pharmacokinetic parameters of EXP3174 after single and multiple doses of AI were a mean maximum concentration in plasma (Cmax ) of 2242 ± 1037 ng/mL and median time to reach Cmax (Tmax ) of 3.5 hours (2.5-8 hours). The median Tmax, at steady state was 4.0 hours (1.5-8 hours). The mean Cmax at steady state (Cmax, SS ) was 2047 ± 1050 ng/mL. In terms of EXP3174, there was no significant difference in the Cmax, SS , area under the curve from time zero to 24 hours of quantifiable concentration at steady state (AUC0-24 SS ), and AUC0-72 after multiple doses of AI. Serious adverse events did not occur. These data suggest that AI is safe and well tolerated in healthy Chinese individuals at a single dose of 480 or 480 mg once daily for 7 days.