Background and purpose: Spironolactone is a potassium-sparing diuretic and is a competitive antagonist of aldosterone, which is widely used in the treatment of primary aldosteronism, essential hypertension, congestive cardiac failure, and various edematous states. The purpose of this study was to compare the pharmacokinetic properties and bioequivalence of the two formulations of spironolactone tablets in healthy Chinese male subjects under fasting and fed condition.
Methods: A total of 40 male subjects were enrolled in this randomized, open-label, two-period crossover study, subjects in 2 groups (20 individuals in each group) received a single 100-mg dose of test or reference spironolactone tablet formulations with a 2-week washout period under both fasting and fed condition. The plasma concentrations of canrenone, a major active metabolite of spironolactone, were quantified by a validated high performance liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters including AUC0-tlast, AUC0-∞, tmax, and Cmax were employed to test bioequivalence.
Results: The relative bioavailability was 99.2 ± 11.6% and 97.6 ± 7.4% under fasting and fed condition, respectively. The 90% confidence intervals of the adjusted geometric mean ratio (test/reference) of Cmax, AUC0-tlast, and AUC0-∞ were 89.7-113.8%, 93.9-103.3%, and 90.0-103.0% in fasting study and 87.7-102.3%, 95.1-99.5%, and 94.1-98.9% in fed study, respectively.
Conclusions: Based on pharmacokinetic parameters and the Chinese Food and Drug Administration's guidance and regulatory criteria for bioequivalence, the test and reference formulations of spironolactone were bioequivalent under both fasting and fed condition. Both formulations were generally well tolerated, with no adverse reaction reported.