Spironolactone. II. Bioavailability

The bioavailability of commercial 25‐mg spironolactone tablets and a new tablet preparation containing 100 mg of the drug has been determined in 12 healthy male subjects. After a 200‐mg oral dose of the drug given in a solution of polyethylene glycol‐400, the peak plasma level of the dethioacetylated metabolite canrenone was 633 ± 154 ng Iml (mean ± SD) and was reached at 1.4 ± 0043 hr. This peak was higher and was achieved earlier than after either eight 25‐mg tablets (480 ± 155 ng/ml at 2.9 ± 1.03 hr) or two 100‐mg tablets (474 ± 182 ng/ml at 3.0 ± 1.37 hr). From the ratio of the 24‐hr area under the plasma concentration‐time curves, the bioavailabilities of the two tablet preparations relative to the solution were 99.6 ± 18.2% and 92.1 ± 22.9%, respectively. The amount of canrenone excreted in the urine by 48 hr was 4048 ± 1.26 mg (solution), 6.36 ± 2.02 mg (eight 25‐mg tablets), and 7.81 ± 1.87 mg (two 100‐mg tablets), representing 2% to 4% of the administered dose. It is concluded that urinary excretion of canrenone alone is not a reliable method for determining the bioavailability of spironolactone.