Effect of multiple doses of fimasartan, an angiotensin II receptor antagonist, on the steady-state pharmacokinetics of digoxin in healthy volunteers.

Author(s): Yi S, Kim JW, Kim TE, Kim J, Jun YK, Choi J, Yoon SH, Cho JY, Song SH, Shin SG, Jang IJ, Yu KS

Affiliation(s): Department of Pharmacology and Clinical Pharmacology, Seoul, Republic of Korea.

Publication date & source: 2011-05, Int J Clin Pharmacol Ther., 49(5):321-7.

Publication type: Clinical Trial; Research Support, Non-U.S. Gov't

Fimasartan (BR-A-657) is an angiotensin II receptor antagonist, recently approved as an antihypertensive agent. Objective: This study aimed to investigate whether administration of fimasartan has an effect on the steady-state pharmacokinetics of digoxin. Methods: An open-label, two-period, two-treatment, single-sequence, crossover study was conducted in 14 healthy male volunteers. On the first day of each 7-day treatment period, subjects received a loading dose of digoxin 0.5 mg, either alone or together with fimasartan 240 mg in the morning, followed by an additional dose of digoxin 0.25 mg after 6 h. On the subsequent 6 days, digoxin 0.25 mg, either alone or with fimasartan 240 mg was administered once daily. Serial blood samples for pharmacokinetics were collected up to 24 h after the last administration in each period. Results: The geometric mean ratio and 90% confidence intervals (CI) for the Cmax,ss and AUCtau,ss of digoxin (with/without fimasartan) were 1.307 (1.123 - 1.520) and 1.087 (1.015 - 1.165), respectively. Study medications were well-tolerated without serious adverse events or clinically meaningful changes. Conclusions: Coadministration of fimasartan with digoxin does not result in clinically significant changes of digoxin pharmacokinetics at steady-state in healthy subjects.