Liposomal amphotericin B (AmBisome®) application and hepatic microsomal enzyme function in the rat

In the present study we investigated the influence of AmBisome®, a lyophilized liposomal amphotericin B formulation on various hepatic cytochrome P450‐dependent mixed function oxidases, antipyrine clearance and hepatic glucose‐6‐phosphatase activity in rats. Animals were treated intravenously for 6 ...

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Published in:	Mycoses Vol. 42; no. 7-8; pp. 459 - 463
Main Authors:	Inselmann, G., Schimanski, Anna, Jahns, R., Heidemann, H. T.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Science Ltd 01-09-1999 Blackwell
Subjects:	Amphotericin B - administration & dosage Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antifungal agents Antifungal Agents - administration & dosage Biological and medical sciences Male Medical sciences Microsomes, Liver - drug effects Microsomes, Liver - enzymology Mixed Function Oxygenases - metabolism Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Intravenous administration Rat Enzyme Cytochrome P450 Rodentia Oxidase Phosphoric monoester hydrolases Liposome Esterases Biological activity Liver function Vertebrata Experimental disease Mammalia Amphotericin B Polyenic compound Animal Dosage form Hydrolases Oxidoreductases Phenazone Glucose-6-phosphatase
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Summary:	In the present study we investigated the influence of AmBisome®, a lyophilized liposomal amphotericin B formulation on various hepatic cytochrome P450‐dependent mixed function oxidases, antipyrine clearance and hepatic glucose‐6‐phosphatase activity in rats. Animals were treated intravenously for 6 days with AmBisome (15 mg kg−1 body weight). Subsequently, the enzyme activities and cytochrome P450 concentrations were measured ex vivo in hepatic microsomes. Following AmBisome the activity of the microsomal ethoxycoumarin‐O‐deethylase increased significantly from 333±77 pmol mg−1 to 459±125 pmol mg−1, whereas benzpyrenhydroxylase and glucose‐6‐phosphatase did not change compared with the controls. Accordingly, antipyrine clearance was not affected by AmBisome treatment. Microsomal cytochrome P450 concentrations as well as total microsomal protein concentrations were not changed following treatment with AmBisome and it did not affect either serum levels of liver transaminases or bilirubin. The results show that the application of a high AmBisome dose had no adverse effects on a variety of microsomal hepatic enzymes and the antipyrine clearance in rats. Thus, it seems likely that AmBisome does not seriously impair metabolic liver function.
Bibliography:	ArticleID:MYC506 ark:/67375/WNG-H9282P4B-Z istex:C89C5623FBB1BD48E248A950707870ACAADC2D3A ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0933-7407 1439-0507
DOI:	10.1046/j.1439-0507.1999.00506.x