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托拉塞米耳毒性的定量评估。

Quantitative assessment of torasemide ototoxicity.

作者信息

Klinke R, Mertens M

机构信息

Zentrum der Physiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt/Main, Fed. Rep. of Germany.

出版信息

Arzneimittelforschung. 1988 Jan;38(1A):153-5.

PMID:3370060
Abstract

Torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea), a new loop diuretic, was quantitatively tested for ototoxicity in cats. The toxic dose that causes a defined hearing loss in 50% of the animals (TD50) was determined. TD50 was calculated as 20.8 mg/kg. This is slightly but not significantly above the value for furosemide (18.37 mg/kg). Hearing function tended to recover after the acute effect. The main metabolite in man (1-isopropyl-3-([(3-carboxy-anilino)-3-pyridyl]sulfonyl)urea, M5) showed no ototoxic action even in excessive doses. To ensure complete recovery, hearing function was tested in animals pretreated with torasemide in doses higher than TD50. There was no indication for permanent hearing impairment in these pretreated animals.

摘要

托拉塞米(1-异丙基-3-([4-(3-甲基苯氨基)吡啶]-3-磺酰基)脲)是一种新型袢利尿剂,对猫进行了耳毒性定量测试。测定了导致50%的动物出现明确听力损失的毒性剂量(TD50)。TD50计算为20.8mg/kg。这略高于呋塞米的值(18.37mg/kg),但无显著差异。急性作用后听力功能有恢复趋势。人体中的主要代谢产物(1-异丙基-3-([(3-羧基苯胺基)-3-吡啶基]磺酰基)脲,M5)即使大剂量使用也无耳毒性作用。为确保完全恢复,对用高于TD50剂量的托拉塞米预处理的动物进行了听力功能测试。这些预处理动物未出现永久性听力损害迹象。

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