Study on the bioequivalence of two formulations of eplerenone in healthy volunteers under fasting conditions: data from a single-center, randomized, single-dose, open-label, 2-way crossover bioequivalence study.

BACKGROUND

Eplerenone (CAS 107724-20-9) prevents the binding of aldosterone, a key hormone in the renin-angiotensin-aldosterone-system (RAAS), which is involved in the regulation of blood pressure and the pathophysiology of cardiovascular disease and is indicated, in addition to standard therapy including beta-blockers, to reduce the risk of cardiovascular mortality and morbidity in stable patients with left ventricular dysfunction (LVEF < or = 40%) and clinical evidence of heart failure after recent myocardial infarction.

OBJECTIVE

The aim of this study was to assess the bioequivalence of a new eplerenone 50 mg formulation (test formulation) vs. the reference product, as required by European regulatory authorities for the marketing of a generic product.

METHODS

This was a single-center, randomized, single-dose, open-label, 2-way crossover study in healthy volunteers under fasting conditions. Plasma samples were collected up to 24 h post-dosing and plasma eplerenone levels were determined by reversed phase high performance liquid chromatography and by tandem mass spectrometry detection (ie, the LC-MS/MS method). Pharmacokinetic parameters were calculated using non-compartmental analysis. Area under the concentration-time curve from time zero to time of last non-zero concentration (AUClast) and maximum observed concentration (Cmax) were the main evaluation criteria. All of the above-mentioned pharmacokinetic parameters were analyzed using 90% geometric confidence interval of the ratio (T/R) of least-squares means from the ANOVA of the 1n-transformed parameter. Tolerability was monitored using physical examination, including vital sign measurements and laboratory analysis.

RESULTS

According to the classical approach, the 90% geometric confidence intervals obtained by analysis of variance for AUClast and Cmax were within the predefined ranges (80.00-125.00%).

CONCLUSION

Bioequivalence between test and reference formulations, both in terms of rate and extension of absorption, under fasting conditions was concluded according to European guidelines. Both formulations were well tolerated.