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Genetic Differences in Drug Disposition
Author(s) -
May D. Gail
Publication year - 1994
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1994.tb04001.x
Subject(s) - enzyme , xenobiotic , drug , biology , genetic variation , drug metabolism , isozyme , genetic variability , genetics , pharmacology , genotype , biochemistry , gene
Genetic polymorphisms of drug metabolizing enzymes are well recognized. This review presents molecular mechanisms, ontogeny and clinical implications of genetically determined intersubject variation in some of these enzymes. Included are the polymorphic enzymes N‐acetyl transferase, cytochromes P4502D6 and 2C, which have been well described in humans. Information regarding other Phase I and Phase II polymorphic pathways, such as glutathione and methyl conjugation and alcohol and acetaldehyde oxidation continues to increase and are also discussed. Genetic factors effecting enzyme activity are frequently important determinants of the disposition of drugs and their efficacy and toxicity. In addition, associations between genetic differences in these enzymes and susceptibility to carcinogens and teratogens have been reported. Ultimately, the application of knowledge regarding these genetic factors of enzyme activity may guide medical therapy and minimize xenobiotic‐induced disease.