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Title: Review article: hypoxia and hepatic drug metabolism--clinical implications.
Austin Authors: Angus, Peter W ;Morgan, Denis J;Smallwood, R A
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Jun-1990
Publication information: Alimentary Pharmacology & Therapeutics; 4(3): 213-25
Abstract: Most major pathways of hepatic drug metabolism are dependent on oxygen. Hepatic mixed-function oxidases use oxygen directly as a substrate, while many other enzyme systems are indirectly dependent on oxygen for the generation of essential co-factors, such as NAD+ and ATP. Studies in vitro show that many of these oxygen-dependent reactions are impaired by relatively minor reductions in oxygen supply, of a magnitude likely to be encountered in vivo. Phase I metabolism by mixed-function oxidases appears to be more sensitive to hypoxia than phase II drug conjugation, although the oxygen requirements of conjugation reactions, such as glucuronidation, may be greatly enhanced by poor nutrition or fasting. Studies in humans are few, but in general they affirm the potential importance of the effects of hypoxaemic states on hepatic drug elimination. On present evidence, special care should be taken in hypoxic patients with drugs extensively metabolized by the liver, particularly those which have a low therapeutic ratio.
Gov't Doc #: 2104086
Type: Journal Article
Subjects: Animals
Pharmaceutical Preparations.metabolism
Appears in Collections:Journal articles

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