Pharmacokinetics of spironolactone and potassium canrenoate in humans.

Plasma concentrations and urinary excretion of canrenone (III), canrenoic acid (IV) and canrenoic acid glucuronide (V) were determined by means of high performance liquid chromatography (HPLC) and fluorometry after oral administration of spironolactone (I) and potassium canrenoate (II) to human subjects. Comparison of both assays for III in plasma as well as in urine after administration of I showed marked differences. Plasma concentrations of III were significantly higher after administration of II than I, Cmax and AUC from II being 3--5 times larger than those from I by means of HPLC assay, while the fluorometrically determined values for III in plasma after administration of I and II did not differ as much from each other. On the other hand, in contrast to plasma, the amount of III excreted in urine after administration of I was much larger than that after II, i.e. 3--4 times greater by means of HPLC and over 10 times greater by means of fluorometry. These results strongly suggest that precursors of III are formed which have a higher renal clearance than that for III alone after oral administration of I. Considering the relative biological potency ratio of I and II, it is presumed that their pharmacological activities may relate to the urinary excretion of III. Plasma concentrations of IV were definitely higher after administration of II compared to those after I. Canrenoic acid (IV) was excreted mainly as glucuronide (V) in urine.