Investigation on the bioequivalence of 2 oral preparations containing spironolactone and furosemide

The bioequivalence of 2 formulations containing spironolactone and furosemide was determined. The test preparation was Spironolacton 50 plus Heumann tablets, a new generic spironolactone preparation, developed by Heumann Pharma GmbH, the reference preparation was Osyrol 50-Lasix capsules, Hoechst AG. The study was designed as a randomized 2-period, 2-sequence, crossover study. A daily dose of 50 mg spironolactone and 20 mg furosemide was administered over 5 days to 24 healthy volunteers in the fasting state. Plasma samples were assayed for spironolactone, its 2 active metabolites canrenone and 7alpha-thiomethylspirolactone, and furosemide by HPLC. Statistical analysis was performed by ANOVA and by nonparametric methods. Because spironolactone was rapidly eliminated from plasma, its pharmacokinetics could only be evaluated with regard to maximum plasma levels. This parameter did slightly miss the criteria for bioequivalence. For canrenone and 7alpha-thiomethylspirolactone bioequivalence was given. For furosemide the test formulation was found to be equivalent concerning the extent of bioavailability. Bioequivalence with regard to maximum concentrations could not be shown. However, from the point of view of pharmacodynamics, this finding may not necessarily be of clinical relevance.