Y. Choi,1 J. Ghim,2 E. Sim,1 S. Park,1 S. Baek,3 J. Shin2; 1Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea, Republic of, 2Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine; Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea, Republic of, 3Boryung Pharmaceutical Corp, Ltd. Republic of Korea., Seoul, Korea, Republic of

BACKGROUND: Fimasartan is a selective antagonist of the angiotensin II AT1-receptor and lowers the blood pressure in hypertensive patients. The goal of this study was to determine the absolute bioavailability of an oral dose of fimasartan.
METHODS: A randomized, open-label, 2-way crossover study was conducted in healthy male volunteers. Each volunteer was administered a single oral dose of fimasartan 60 mg in one period, and a single intravenous (IV) infusion of 30 mg fimasartan for 1 hour in the other period, with one week washout period. Pharmacokinetic and tolerability assessments were conducted up to 48 hours after dosing. Fimasartan plasma concentrations were analyzed by validated LC/MS/MS method.
RESULTS: Sixteen Korean male volunteers aged 21-29 years entered and completed the trial. Their mean height was 174 cm (range, 165-181 cm), and their mean body weight was 68.8 kg (range, 53.3-80.4 kg). The absolute oral bioavailability of fimasartan was estimated to be 18.6%. After fimasartan 60 mg single oral dose administration, fimasartan was rapidly absorbed and reached maximum plasma concentration at approximately 3 hours (range, 0.50-5.00). After reaching this point, the drug concentration decreases with an elimination half-life of approximately 5.8 hours. When fimasartan 30 mg was administered via IV infusion over 1 hour, the disposition of fimasartan after dosing was characterized by biphasic decay kinetics, with a distribution phase (half-life 0.25 h), followed by a longer elimination phase (half-life 5.5 h). The mean volume of distribution at steady state was 42.4 L, and the total body clearance 39.0 L/h.
CONCLUSION: The absolute oral bioavailability of fimasartan was approximately 19%. Single oral and intravenous doses of fimasartan were well tolerated by study volunteers.