In a preliminary open bioequivalence investigation of orientating character (n =4) a single 100 mg dose of spironolactone (study I) led to maximum canrenone plasma levels (determined by HPLC) of 126.5 +/- 28.4 ng/ml (standard formulation 1) and 130 +/- 13.1 ng/ml (test formulation 2). The corresponding values for the sum of the fluorogenic metabolites were 418.9 +/- 43.5 ng (eq)/ml formulation 1 and 469.9 +/- 80.3 ng (eq)/ml formulation 2. A comparison of AUCs for both total fluorogenic metabolites and canrenone showed no marked differences. In a 2nd cross-over bioequivalence study with multiple dosing, mean minimum steady-state levels of 102.5 +/- 14 ng/ml (formulation 1) and 98.1 +/- 14.1 ng/ml (formulation 2) were obtained for canrenone, and 389 +/- 35.8 ng (eq)/ml (formulation 1) and 391.4 +/- 18.9 ng (eq)/ml (formulation 2) for total fluorescence. The AUCs for post-steady-state elimination, starting with the final spironolactone dose on day 10, were comparable. They were calculated to be 13226 +/-828 ng (eq)/ml . h (formulation 1) and 13858 +/- 651 ng (eq)/ml . h (formulation 2) for total fluorescence, and 3222 +/- 217 ng/ml (formulation 1) and 3167 +/- 195 ng/ml (formulation 2) for canrenone. Both spironolactone formulations can be considered as bioequivalent. The elimination half-lives (t 1/2) after a single 100 mg dose of spironolactone are (Study I) 16.4--19.1 h for canrenone and 13.6--14.0 h for the sum of the active (i.e., antagonistic to aldosterone) metabolites. Certain therapeutic conditions (e.g. multiple dosing of 100 mg spironolactone with tau = 12 h, Study II) can lead to slightly increased t 1/2 values for both canrenone (18.6--21.4 (h)) and total fluorogenic metabolites (15.8--16.9 (h)). The steady-state level for both formulations is reached by the third day of treatment.