INVESTIGATION ON THE BIOEQUIVALENCE OF 2 ORAL PREPARATIONS CONTAININGSPIRONOLACTONE AND FUROSEMIDE

The bioequivalence of 2 formulations containing spironolactone and fur osemide 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 volunteer s in the fasting state. Plasma samples were assayed for spironolactone , its 2 active metabolites canrenone and 7 alpha-thiomethylspirolacton e, and furosemide by HPLC. Statistical analysis was performed by ANOVA and by nonparametric methods. Because spironolactone was rapidly elim inated 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 7 alpha-thiomethylspiro lactone bioequivalence was given. For furosemide the test formulation was found to be equivalent concerning the extent of bioavailability. B ioequivalence with regard to maximum concentrations could not be shown . However, from the point of view of pharmacodynamics , this finding m ay not necessarily be of clinical relevance.