Karim A, Kook C, Zitzewitz D J, Zagarella J, Doherty M, Campion J
Drug Metab Dispos. 1976 Nov-Dec;4(6):547-55.
The absorption, excretion and metabolism of [22-14C]spironolactone was compared in Charles River rats, beagle dogs and rhesus monkeys. The drug was administered at the fixed dose of 5 mg/kg po and iv. From the po/iv ratios of the areas under the plasma radioactivity-time curves, the gastrointestinal absorption of the drug was estimated to be 82% in the rat, 62% in the dog, and 103% in the monkey. The absolute bioavailability of a pharmacologically active metabolite, canrenone, was 57% in the dog and 48% in the monkey. Spironolactone was extensively metabolized in all three species and differences existed in the composition of the metabolites in their plasma, urine, and feces. The amount of radioactivity that was excreted in the urine and feces of all three species was similar after either po or iv administration of the drug. The cumulative average excretion of radioactivity in the urine as percentage of the po dose in 6 days was 4.69% in the rat (N = 5), 18.5% in the dog (N = 3), and 46.0% in the monkey (N = 3). In the feces, the corresponding excretion values were 74.2, 69.3 and 40.1%, respectively. Canrenone excretion in the urine constituted 0.65% of the po dose in the rat, 0.82% in the dog, and 5.86% in the monkey, whereas the excretion of total fluorogenic metabolites constituted 1.1, 1.9, and 12.1% respectively. Comparison of animal data with those published for humans indicated that the disposition and metabolism of spironolactone in the rhesus monkey, rather than those in the rat or the dog, was closest to that in man.
对[22-14C]螺内酯在查尔斯河大鼠、比格犬和恒河猴体内的吸收、排泄及代谢情况进行了比较。该药物经口服和静脉注射的固定剂量均为5 mg/kg。根据血浆放射性-时间曲线下面积的口服/静脉注射比值，估计该药物在大鼠体内的胃肠道吸收率为82%，在犬体内为62%，在猴体内为103%。药理活性代谢物坎利酮的绝对生物利用度在犬体内为57%，在猴体内为48%。螺内酯在所有三个物种中均被广泛代谢，且它们血浆、尿液和粪便中代谢物的组成存在差异。在口服或静脉注射该药物后，所有三个物种尿液和粪便中排出的放射性量相似。6天内尿液中放射性的累积平均排泄量占口服剂量的百分比，大鼠为4.69%（N = 5），犬为18.5%（N = 3），猴为46.0%（N = 3）。在粪便中，相应的排泄值分别为74.2%、69.3%和40.1%。尿液中坎利酮的排泄量占大鼠口服剂量的0.65%，犬为0.82%，猴为5.86%，而总荧光代谢物的排泄量分别为1.1%、1.9%和12.1%。将动物数据与已发表的人类数据进行比较表明，恒河猴体内螺内酯的处置和代谢情况比大鼠或犬更接近人类。
