Pharmacokinetic and safety profile of olmesartan medoxomil in healthy Chinese subjects after single and multiple administrations.

The primary aim of this study was to investigate the pharmacokinetics and safety of daily oral doses of olmesartan medoxomil administered to healthy Chinese subjects for 7 days. All 14 subjects (8 males/6 females) received a single dose of 20 mg olmesartan medoxomil and followed by multiple oral doses of 20 mg olmesartan medoxomil once daily for 7 days. Blood and urine samples were obtained for a 48-h pharmacokinetic evaluation on two PK days (Day 1 and Day 9). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were determined at the scheduled time for safety evaluation. The concentration of RNH-6270 (olmesartan, the unique available metabolite of olmesartan medoxomil in vivo) in plasma and urine were determined with HPLC-MS/MS method after solid-phase extraction. Pharmacokinetic parameters tmax, Cmax, t 1/2, AUC (0, 24 h), AUC(0-infinity), and CLr of RNH-6270 were derived from the concentration-time profiles for single- and multiple-dose administration. The pharmacokinetic parameters were summarized by gender and treatment factors which were tested by ANOVA. The results showed that there was no significant difference between male and female. Safety results showed that the decrease of blood pressure was consistent with increase of concentration of RNH-6270 and heart rate was consistent. Based above analysis, it was concluded that olmesartan medoxomil 20 mg was safe and there were no any accumulation in healthy Chinese subjects after multiple-dose.