PP.LB01.25

Abstract

Objective: Fimasartan, a novel potent angiotensin receptor blocker, was developed by Boryung Pharmaceutical. Co. Ltd in Korea. Considering that Korean patients were studied in pivotal clinical trials, determination of Fimasartan pharmacokinetic (PK) parameters in Russian patients was performed. Design and method: Fifteen adult patients with arterial hypertension grade I-II in one investigational site took a single dose of Fimasartan 60 mg in fasted condition. Blood samples were collected pre-dose, 0,25; 0,5; 1; 1,5; 2; 2,5; 3; 4; 6; 8; 12 and 24 hours post-doses. Plasma concentration of Fimasartan was determined by validated method. Area under concentration-time curve from time zero to last time point (tlast) with measurable concentration (AUC0-tlast), AUC from time zero to infinity (AUC0-inf), percentage of AUC0-inf that is due to extrapolation from tlast to infinity (%AUCextrap), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), apparent terminal elimination half-life (t1/2) were calculated. The results were compared to previously obtained PK data from Korean hypertensive patients and Caucasian healthy volunteers. Results: Following oral administration Fimasartan was rapidly absorbed and after attainment of Cmax, plasma concentrations of Fimasartan appeared to decline in a generally bi-phasic manner. Geometric means of Fimasartan PK parameters and geometric coefficients of variation (CV%) are summarized in Table 1.Fimasartan 60 mg single dose PK parameters in fasted Russian to Korean hypertensive patients were similar: median tmax occurred approximately 1 h post-dose, ratios for Cmax, AUC0-inf, AUC0-tlast, were 1.10, 0.95 and 0.91, respectively; in Caucasian healthy subjects, tmax occurred 2 hours later than in Russian patients and the ratio for peak exposure (Cmax) was 1.35, total exposure for both populations was similar with AUC0-inf ratio 1.05 and AUC0-tlast ratio 1.08. Conclusions: These findings considerably extended Fimasartan PK data and allowed to extrapolate results of earlier studies, including studies in Korean population, to Russian patients.