阿曲库铵和劳丹诺辛在离体灌注大鼠肝脏中的肝毒性测试。

Hepatotoxicity testing of atracurium and laudanosine in the isolated, perfused rat liver.

作者信息

Reckendorfer H, Burgmann H, Sperlich M, Tüchy G L, Feigl W, Spieckermann P G, Weindlmayr-Göttel M, Schwarz S

机构信息

Department of Pathology, Allgem. Poliklinik, Vienna, Austria.

出版信息

Br J Anaesth. 1992 Sep;69(3):288-91. doi: 10.1093/bja/69.3.288.

DOI:10.1093/bja/69.3.288

PMID:1389846

Abstract

The pharmacokinetics of atracurium, which is degraded by Hofmann decomposition and ester hydrolysis, is not altered by impaired liver function. Atracurium should, therefore, be ideal for patients with heptic failure, and is now widely used in clinical practice. However, some studies reported considerable hepatotoxicity after atracurium, especially from its breakdown products--for example, leakage of lactate dehydrogenase (LDH) from isolated rat hepatocytes. Therefore, we have studied, in an isolated perfused rat liver model, biochemical and morphological changes after administration of either atracurium or its main metabolite, laudanosine. Despite using extremely high concentrations of these substances, we could not detect, biochemically (release of LDH or aspartate amino-transferase (AST)) or histologically, any signs of liver cell damage.

摘要

阿曲库铵通过霍夫曼降解和酯水解作用而降解，其药代动力学不受肝功能损害的影响。因此，阿曲库铵对于肝功能衰竭患者应是理想的药物，目前已在临床实践中广泛应用。然而，一些研究报告称，阿曲库铵用药后有相当大的肝毒性，尤其是来自其分解产物——例如，乳酸脱氢酶（LDH）从离体大鼠肝细胞中泄漏。因此，我们在离体灌注大鼠肝脏模型中研究了给予阿曲库铵或其主要代谢产物劳丹诺辛后的生化和形态学变化。尽管使用了极高浓度的这些物质，但我们在生化方面（LDH或天冬氨酸转氨酶（AST）的释放）或组织学上均未检测到任何肝细胞损伤的迹象。