Relevance of induction of human drug-metabolizing enzymes: pharmacological and toxicological implications.
1. Human drug-metabolizing systems can be induced, or activated, by a large number of exogenous agents including drugs, alcohol, components in the diet and cigarette smoke, as well as by endogenous factors. 2. Such perturbation of enzyme activity undoubtedly contributes to both intra-and inter-individual variation both with respect to the rate and route of metabolism for a particular drug. Induction may, in theory, either attenuate the pharmacological response or exacerbate the toxicity of a particular drug, or both. 3. The clinical impact of enzyme induction will depend upon the number of different enzyme isoforms affected and the magnitude of the inductive response within an individual, and also on the therapeutic indices of the affected substrates. 4. The toxicological implications will be determined either by any change in the route of metabolism, or by a disturbance of the balance between activation and detoxication processes, which may be isozyme selective.
Park
B K
BK
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Kitteringham
N R
NR
Pirmohamed
M
M
Tucker
G T
GT
D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic