Pharmacokinetic Interaction of Fimasartan, a New Angiotensin II Receptor Antagonist, With Amlodipine in Healthy Volunteers

Abstract

Coadministration of fimasartan and amlodipine did not result in clinically relevant changes in the systemic exposure of fimasartan or amlodipine.

Fimasartan: A New Angiotensin Receptor Blocker

“…The authors explained these changes as uremic toxin-and inflammation-mediated decreases of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2) expression and function in the intestine [18]. To aid the development of a single-pill combination, pharmacokinetic studies evaluated the effect of co-administration of fimasartan with amlodipine or hydrochlorothiazide on the steady-state pharmacokinetics of each drug in healthy volunteers; no significant interactions were shown [19,20]. In addition, no significant drug interactions were observed when fimasartan was used in combination with warfarin or digoxin in healthy volunteers [21,22].…”

“…Based on the phase I pharmacokinetic study that confirmed no significant interactions with amlodipine on the steadystate pharmacokinetics of each drug in healthy volunteers when co-administered [19], the phase II, randomized, multicenter, double-blind, placebo-controlled, 3 9 3 factorial-designed study was performed to evaluated the effect on BP reduction of single or combined administration of fimasartan at three doses (0, 30, and 60 mg) and amlodipine at three doses (0, 5, and 10 mg) for 8 weeks. In patients with essential hypertension whose DBP was between 90 and 114 mmHg after a 2-week placebo run-in period, all treatment groups produced significantly greater BP reductions than the placebo group.…”

Pharmacological Profiles of a Highly Potent and Long-Acting Angiotensin II Receptor Antagonist, Fimasartan, in Rats and Dogs after Oral Administration

“…When the blood pressure and heart rate were stabilized, Ang II (0.1 µg/kg) was intravenously administered to the left femoral vein of rats three times with an interval of 20 min prior to treatment of test compounds to obtain the reference. Fimasartan (0.3, 1, or 3 mg/kg), losartan (1, 3, or 10 mg/kg) or vehicle distilled water (D.W.) were administered orally and then Ang II were intravenously treated as a bolus at various time points (20,40, 60 min, 1.5, 2, 3, 4, 5,6,8,10,12,16,20, and 24 h) to determine the Ang II-induced blood pressure response.…”

“…Co., Ltd., Seoul, Republic of Korea) was approved by the Korea Food and Drug Administration (KFDA) in 2010 for the treatment of essential hypertension. Several nonclinical and clinical studies have been conducted on fimasartan, for example, (1) clinical studies have been undertaken on its efficacy and safety in large populations 8,9) and interactions with other concomitant drugs [10][11][12] and (2) nonclinical studies have investigated the mechanistics underlying its other pharmacological activities, such as, its inhibitory effect on catecholamine secretion, 13) its cardioprotective effect, which was attributed to the prevention of mitochondrial damage, 14) its anti-atherosclerotic effect, 15) and its anti-inflammatory potential.…”

Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of Fimasartan in Rats, Dogs, and Humans

“…In contrast to other ARBs, fimasartan did not show partial agonistic effects on the angiotensin II receptor in animal models (13). Consequently, phases II and III studies demonstrated a higher potency and stronger efficacy of fimasartan compared with losartan with a rapid onset of antihypertensive effect (14,15). Jürgen B. Bulitta and Beom Soo Shin contributed equally to this work.…”