Delarge J
Department of Medicinal Chemistry, State University of Liège, Belgium.
Arzneimittelforschung. 1988 Jan;38(1A):144-50.
Out of a series of pyridine-3-sulfonylureas with diuretic activity torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) has been proved to be one of the most active derivatives. In the rat, urinary volume and electrolyte excretions increased linearily with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. Experiments by oral and intravenous routes indicated that torasemide was equally potent both by oral and parenteral administration. Compared to furosemide, torasemide was 9-40 times more potent on weight basis in the rat. For the same natriuretic effect, however, potassium losses with torasemide were significantly less than with furosemide. The diuretic effect of torasemide lasted longer compared to that of furosemide. In accordance with the pharmacodynamic characteristics plasma elimination half-life of torasemide was about 1.5 h in the rat and bioavailability was nearly complete. Torasemide was 98-99% bound to plasma proteins. No in vitro interaction was found with the cumarine derivative warfarin.
在一系列具有利尿活性的吡啶 - 3 - 磺酰脲类药物中，托拉塞米（1 - 异丙基 - 3 - ([4 - (3 - 甲基 - 苯基氨基)吡啶] - 3 - 磺酰)脲）已被证明是活性最强的衍生物之一。在大鼠中，尿量和电解质排泄量随剂量的对数呈线性增加，因此类似于高效能利尿剂的特征。经口服和静脉途径的实验表明，托拉塞米口服和胃肠外给药的效力相同。与呋塞米相比，托拉塞米在大鼠中按重量计算效力高9至40倍。然而，对于相同的利钠作用，托拉塞米导致的钾流失明显少于呋塞米。与呋塞米相比，托拉塞米的利尿作用持续时间更长。根据药效学特征，托拉塞米在大鼠中的血浆消除半衰期约为1.5小时，生物利用度几乎完全。托拉塞米与血浆蛋白的结合率为98 - 99%。未发现与香豆素衍生物华法林有体外相互作用。
