CHOLESTASIS IN THE RAT BY MEANS OF INTRAVENOUS ADMINISTRATION OF CYCLOSPORINE VEHICLE, CREMOPHOR EL
作者:
IRENE ROMAN,
MARIA MONTE,
ALEJANDRO ESTELLER,
RAFAEL JIMENEZ,
期刊:
Transplantation
(OVID Available online 1989)
卷期:
Volume 48,
issue 4
页码: 554-558
ISSN:0041-1337
年代: 1989
出版商: OVID
数据来源: OVID
摘要:
The effect of cyclosporine vehicle, Cremophor EL, on bile flow and biliary bile acids and bilirubin output was studied in anesthetized male Wistar rats. Intravenous administration of Cremophor EL or castor oil as a single bolus reduced bile flow and the biliary output of bile acids and bilirubin. The Cremophor EL-induced cholestasis was an immediate and reversible phenomenon, since at 30–35 min after drug injection all parameters evaluated had returned to control values. A slight increase in serum bilirubin concentrations was observed. Our data indicate that the observed cholestasis is related to a reduction in both bile acid-dependent and bile acidindependent bile flow, probably due to a transitory hepatotoxic effect of Cremophor EL. We conclude that the clinically used vehicle for i.v. administration of cyclosporine, Cremophor EL, has adverse effects on hepatobiliary physiology in the rat and suggest that an alternative vehicle should be used.
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