Dose Proportionality and Pharmacokinetics of Eplerenone in Healthy Chinese Subjects

BACKGROUND: Eplerenone (CAS 107724-20-9) is the first highly selective aldosterone receptor blocker and is used worldwide for treatment of hypertension and heart failure. OBJECTIVE: The objective of this study was to investigate the eplerenone pharmacokinetics in healthy Chinese subjects and assess the dose proportionality over the therapeutic dose range. METHODS: A single-dose, randomized, 6-sequence, 3-treatment, 3-period crossover, open label study was conducted in 12 healthy Chinese subjects, who received 3 doses of eplerenone in random order (25, 50, 100 mg). The power model was used to evaluate the dose proportionality of eplerenone. The pharmacokinetic study of multiple-dose of eplerenone was also conducted. RESULTS: After single-dose oral administration, the mean C max value increased from 489 to 1 641 ng/mL, and the mean AUC 0-t value increased from 3 030 to 10 893 ng/mL·h with an increase in dose from 25 to 100 mg, respectively. The mean value for terminal T 1/2 was approximate 3 h with no significant differences among different dose groups. Though dose proportionality of eplerenone was inconclusive in Chinese subjects over the dose range of 25-100 mg, the maximal proportionality dose range (ρ1) was 2.06 based on power model. Steady state could achieve within at least 4 days and no accumulation was observed after multiple-dose of eplerenone. CONCLUSION: Dose proportionality was inconclusive in over the dose range of 25-100 mg; however, linear pharmacokinetics could be considered when dose ratio is no more than 2.06.