Format

Send to

Choose Destination
See comment in PubMed Commons below
Xenobiotica. 1990 Nov;20(11):1171-85.

Assessment of enzyme induction and enzyme inhibition in humans: toxicological implications.

Author information

  • 1Department of Pharmacology and Therapeutics, University of Liverpool, UK.

Abstract

1. The principal methods used for the assessment of enzyme induction and enzyme inhibition are measurement of the pharmacokinetics of a model compound (probe drug), analysis of drug metabolism in vitro, and determination of changes in the disposition of, and endogenous substrate for, the enzyme of interest. 2. Probe drugs that have been used for this purpose include antipyrine, aminopyrine, tolbutamide, caffeine, theophylline, warfarin, oxazepam and paracetamol. Measurement of the excretion of metabolites of cortisol and oestradiol, which are endogenous substrates for cytochrome P450 IIIA enzymes, provides a non-invasive means of assessing enzyme induction or inhibition. 3. Combined pharmacokinetic/pharmacodynamic studies are required to assess the pharmacological relevance of either induction or inhibition of the enzymes involved in drug metabolism. 4. At present it is difficult to assess the toxicological implications of enzyme induction and inhibition in man. Safe probe drugs are required for the enzymes primarily responsible for drug detoxication, such as epoxide hydrolase and glutathione transferase, in order to identify individuals particularly at risk.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Taylor & Francis
    Loading ...
    Write to the Help Desk