Abshagen U, Rennekamp H, Luszpinski G
Naunyn Schmiedebergs Arch Pharmacol. 1976 Dec;296(1):37-45. doi: 10.1007/BF00498838.
Five healthy male volunteers received 500 mg Aldactone orally together 100 muCi 3H-20-21-spironolactone; one elderly patient received 1 mCi 3H-spironolactone without additional 'cold' drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25-40 min after administration amounting to 2-3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t 1/2: 2.57 +/- 0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t 1/2: 1.66 +/- 0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47-57% of the dose were excreted in urine and the remaining amount could be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t 1/2: 0.9 +/- 0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7 alpha-methylsulfonyl-6 beta, 17 beta-dihydroxy-4-androsten-17 alpha-yl) propionic acid gamma-lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6 beta-OH-7 alpha-methylsulfinyl-spirolactone leveled off and seemed to be and endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.
5名健康男性志愿者口服500毫克安体舒通，并同时服用100微居里的3H-20-21-螺内酯；1名老年患者服用1毫居里的3H-螺内酯，未加用其他“非放射性”药物。在6天时间里，对药物在血浆、尿液和粪便中的处置动力学进行了研究。给药后25至40分钟，血浆中的氚浓度达到峰值，相当于剂量的2%至3%/升。直至第12小时，其迅速下降，并在第36至96小时之间呈单指数下降（半衰期：2.57±0.27天）。之后，观察到血浆中放射性物质消除速度显著加快（半衰期：1.66±0.21天）。血浆中标记物的生物半衰期长于荧光化合物。47%至57%的剂量经尿液排出，其余部分可在粪便中检测到（总回收率90%）。尿液排泄率的半衰期明显短于血浆中总放射性的半衰期（半衰期：0.9±0.11天）。这一点，再加上观察到尿液中极性部分从35%增加到85%，同时血浆中从55%下降到35%，提示存在亲脂性化合物的肾小管重吸收或肠肝循环。尿液中亲脂性部分的薄层层析分离显示出两种先前未知的化合物，其中主要同系物被鉴定为3-(3-氧代-7α-甲基磺酰基-6β,17β-二羟基-4-雄甾烯-17α-基)丙酸γ-内酯，以及坎利酮和已描述的代谢产物（卡里姆和布朗，1972年；卡里姆等人，1975年）。这种代谢产物是最初几小时内尿液中主要的亲脂性降解产物，而6β-OH-7α-甲基亚磺酰基-螺内酯趋于平稳，似乎是一种终末排泄产物。为了进一步表征，对极性部分进行了酸性水解。讨论了螺内酯降解的已知代谢途径。
