Kido H, Ohtaki Y
Welfide Corporation, Drug Development Laboratories, 955 Koiwai, Yoshitomi-cho, Chikujo-gun, Fukuoka 871-8550, Japan.
Nihon Yakurigaku Zasshi. 2001 Aug;118(2):97-105. doi: 10.1254/fpj.118.97.
Loop diuretics potently excrete water and electrolytes and therefore have been widely prescribed for the treatment of various kinds of edema for a long time. The potent diuretic action of loop diuretics, however, often causes hypokalemia, and therefore potassium sparing diuretics have also been supplied as a concomitant drug. Torasemide (LUPRAC), a novel diuretics, shows not only an effective loop diuretic action but also a potassium sparing action due to its anti-aldosteronergic effect. Torasemide also has a high bioavailability and is only slightly influenced by meals in humans. In addition, its pharmacodynamic features contribute to its stable diuretic action without any individual differences. In animal experiments, torasemide showed about a tenfold more potent diuretic action in comparison with furosemide, an authentic loop diuretic. On the one hand, the increase in the urinary potassium excretion by torasemide was relatively slight compared to the increase in urinary sodium excretion and, as a result, the urinary sodium to potassium (Na+/K+) ratio increased. The diuretic profile of torasemide was equal to that of the concomitant use of furosemide and an anti-aldosteronergic drug, spironolactone. Torasemide showed a significant efficacy and safety in comparison with furosemide in the patients with edema in both domestic and foreign clinical studies. Moreover, torasemide also showed a decreased rate of cardiac death in comparison to furosemide in patients with chronic heart failure in a large-scale clinical study (TORIC Study). The difference in cardiac death between these two diuretics has been suggested to depend on the anti-aldosteronergic effect of torasemide. In Japan, no new loop diuretics have been developed in over 10 years. Torasemide is therefore expected to be useful as an effective diuretic for diseases with edema.
袢利尿剂能有效地排泄水和电解质,因此长期以来被广泛用于治疗各种水肿。然而,袢利尿剂强大的利尿作用常常导致低钾血症,因此保钾利尿剂也作为辅助药物使用。托拉塞米(LUPRAC)是一种新型利尿剂,不仅具有有效的袢利尿作用,还因其抗醛固酮作用而具有保钾作用。托拉塞米的生物利用度也很高,在人体中受饮食的影响很小。此外,其药效学特性有助于其产生稳定的利尿作用,且无个体差异。在动物实验中,与传统的袢利尿剂呋塞米相比,托拉塞米的利尿作用强约10倍。一方面,托拉塞米导致的尿钾排泄增加相对于尿钠排泄增加较为轻微,结果尿钠钾(Na+/K+)比值升高。托拉塞米的利尿谱与同时使用呋塞米和抗醛固酮药物螺内酯相当。在国内外临床研究中,与呋塞米相比,托拉塞米在水肿患者中显示出显著的疗效和安全性。此外,在一项大规模临床研究(TORIC研究)中,与呋塞米相比,托拉塞米在慢性心力衰竭患者中还显示出心脏死亡发生率降低。这两种利尿剂在心脏死亡方面的差异被认为取决于托拉塞米的抗醛固酮作用。在日本,10多年来没有研发出新型袢利尿剂。因此,托拉塞米有望成为治疗水肿性疾病的有效利尿剂。