Neugebauer G, Besenfelder E, von Möllendorff E
Department of Clinical Pharmacology, Boehringer Mannheim GmbH, Mannheim, Fed. Rep. of Germany.
Arzneimittelforschung. 1988 Jan;38(1A):164-6.
Torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3- sulfonyl)urea) is a potent new loop diuretic. The pharmacokinetics, absolute bioavailability and metabolic disposition of torasemide have been studied after administration of a standard-release tablet to healthy volunteers. According to a latin square design 9 subjects received in random order single doses of either 20 mg i.v. over 1 h or 20 or 40 mg p.o. On each of the three occasions, torasemide and its metabolites were analysed in plasma and urine up to 24 h. From the results of urinary excretion and plasma AUC, the availability of torasemide from the tablet was 80% to 90%, i.e. nearly complete. The kinetics were linear with dose. The time of peak was reached at 1 h, the elimination half-life varied from 3 h to 4 h. None of the metabolites M1, M3 or M5 found in plasma exhibited a longer half-life. Only a quarter of the low systemic clearance of torasemide (41 ml/min) was accounted for by renal clearance. The distribution volume of 15.5 l was in the order of the extracellular fluid volume. The total amount of torasemide and metabolites recovered in urine was 83%, i.e. 25% torasemide, 11% M1, 3% M3 (both active), and 44% M5 (inactive). Therefore, M1 and M3 probably contribute to the diuretic action of torasemide. Since the renal clearances of the metabolites exceeded that of the parent drug, renal impairment may change their elimination kinetics.
托拉塞米（1-异丙基-3-([4-(3-甲基苯氨基)吡啶]-3-磺酰基)脲）是一种新型强效袢利尿剂。在给健康志愿者服用标准释放片剂后，对托拉塞米的药代动力学、绝对生物利用度和代谢情况进行了研究。根据拉丁方设计，9名受试者按随机顺序分别接受单次静脉注射20mg（1小时内）或口服20mg或40mg。在这三种给药情况下的每一次，均对血浆和尿液中的托拉塞米及其代谢产物进行长达24小时的分析。根据尿排泄结果和血浆曲线下面积（AUC），托拉塞米片剂的生物利用度为80%至90%，即几乎完全吸收。其动力学呈剂量线性关系。1小时达到峰值时间，消除半衰期为3至4小时。在血浆中发现的代谢产物M1、M3或M5的半衰期均未延长。托拉塞米较低的全身清除率（41ml/min）中只有四分之一由肾清除率决定。15.5L的分布容积与细胞外液容积相当。尿液中回收的托拉塞米及其代谢产物总量为83%，即25%为托拉塞米，11%为M1，3%为M3（两者均有活性），44%为M5（无活性）。因此，M1和M3可能对托拉塞米的利尿作用有贡献。由于代谢产物的肾清除率超过母体药物，肾功能损害可能会改变它们的消除动力学。
