N. Gu,1 J. Cho,2 I. Jang,2 M. Rhee3; 1Department of Pharmacology and Therapeutics, Dongguk University College of Medicine and Ilsan Hospital, Goyang, Korea, Republic of, 2Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea, Republic of, 3Cardiovascular Center, Dongguk University College of Medicine and Ilsan Hospital, Goyang, Korea, Republic of

BACKGROUND: Low sodium diet enhances the hemodynamic effect of renin-angiotensin system blockers. In a recent study, the systemic exposure of candesartan and atenolol, substrates of P-glycoprotein (Pgp) or cytochrome P 3A4 (CYP3A4), was reduced by ≈30% on a high-sodium diet, but that of valsartan and ramipril, non-substrates of Pgp or CYP3A4, was not. This study aimed to investigate the effect of high sodium diet on the pharmacokinetics of fimasartan.
METHODS: The study design was a two-diet, two-period, two-sequence, randomized, open label and crossover with 1-week washout for diet. Eligible subjects had either low sodium (50 mEq/day) or high sodium diet (300 mEq/day) for 7 days on the first hospitalization period and had the other diet at the second period. On the seventh morning of each period, subjects received a single dose of fimasartan 60 mg in the fasting state. The pharmacokinetic blood samples were drawn for 24 hours after the administration. The pharmacokinetic parameters were estimated by non-compartmental analysis.
RESULTS: A total of 17 subjects completed the study and one of them had 24-hour urinary sodium values over 100 mEq on low sodium diet. The pharmacokinetic analysis was performed in 16 subjects excluding a noncompliant subject. The geometric mean ratios (high/low sodium diet) and their 90% confidence intervals (CIs) for Cmax, AUC0-24h and AUCinf were 0.84 (0.60-1.18), 0.91 (0.78-1.05) and 0.90 (0.79-1.03), respectively. There were no reports of serious adverse events.
CONCLUSION: The systemic exposure of fimasartan, which is a CYP3A4 substrate but not a Pgp substrate, was slightly (≈10%) lower on high sodium diet than on low sodium diet, but the difference was not significant (>0.05).