Dose Proportionality and Pharmacokinetics of Eplerenone in Healthy Chinese Subjects

Eplerenone (CAS 107724-20-9) is the first highly selective aldosterone receptor blocker and is used worldwide for treatment of hypertension and heart failure.

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.

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.

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.

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.