Overdiek H W, Hermens W A, Merkus F W
Clin Pharmacol Ther. 1985 Oct;38(4):469-74. doi: 10.1038/clpt.1985.206.
Four healthy men took a single oral dose of 200 mg spironolactone after a standardized breakfast. Blood samples were drawn until 24 hours after dosing. A specific HPLC method was used to determine the serum concentrations of spironolactone and its metabolites 7 alpha-thiomethylspirolactone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone, and canrenone. Pharmacokinetic parameters were derived from the serum concentration-time course of each compound. Spironolactone, 7 alpha-thiomethylspirolactone, and canrenone are known to have antimineralocorticoid activity in man. Our study demonstrated that: (1) 7 alpha-Thiomethylspirolactone is the main metabolite of spironolactone after a single oral dose as judged by the AUC(0-24) and the maximum concentration; and (2) unchanged spironolactone was detected in serum, with a maximum concentration at 1 hour and detectable levels up to 8 hours after dosing. Our findings are contrary to the widely accepted belief that spironolactone is metabolized too rapidly to be detected in serum after oral dosing and that canrenone is the principal metabolite of spironolactone.
四名健康男性在标准化早餐后单次口服200毫克螺内酯。给药后采集血样直至24小时。采用特定的高效液相色谱法测定血清中螺内酯及其代谢产物7α-硫甲基螺内酯、6β-羟基-7α-硫甲基螺内酯和坎利酮的浓度。药代动力学参数由每种化合物的血清浓度-时间过程得出。已知螺内酯、7α-硫甲基螺内酯和坎利酮在人体中具有抗盐皮质激素活性。我们的研究表明：（1）根据药时曲线下面积（AUC(0-24)）和最大浓度判断，7α-硫甲基螺内酯是单次口服螺内酯后的主要代谢产物；（2）血清中检测到未代谢的螺内酯，给药后1小时达到最大浓度，给药后8小时仍可检测到。我们的研究结果与广泛接受的观点相反，即认为螺内酯口服给药后代谢太快以至于在血清中无法检测到，且坎利酮是螺内酯的主要代谢产物。
