Hepatotoxicity testing of atracurium and laudanosine in the isolated, perfused rat liver.
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.
Reckendorfer
H
H
Department of Pathology, Allgem. Poliklinik, Vienna, Austria.
Burgmann
H
H
Sperlich
M
M
Tüchy
G L
GL
Feigl
W
W
Spieckermann
P G
PG
Weindlmayr-Göttel
M
M
Schwarz
S
S
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001279:Atracurium / Q000009:adverse effects* / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D007546:Isoquinolines / Q000009:adverse effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats
D007546:Isoquinolines; D001279:Atracurium; C001522:laudanosine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases