| Abstrakt: |
The cytochrome P450 (P450 or CYP) monooxygenases, CYP2D6, CYP2C19 and CYP2C9, display polymorphism. CYP2D6 and CYP2C19 have been studied extensively and, despite their low abundance in the liver, they have been found to catalyze the metabolism of many drugs. CYP2D6 has many allelic variants, whereas CYP2C19 has only seven. Most variants are translated into inactive, truncated proteins or fail to express any protein. There is, as yet, no clear information about the other CYPs (CYP1A1, CYP2A6, CYP2B6, CYP2E1 and CYP3A4/5) polymorphism. When two drugs that are substrates of a polymorphic CYP enzyme are administered concomitantly during drug therapy, each will compete for that enzyme and competitively inhibit the metabolism of the other. This can result in toxicity. Patients who are poor metabolizers (PMs), extensive metabolizers (EMs), and ultrarapid metabolizers (URMs) can be identified. Having such information will help in determining the appropriate dosage of certain drugs when treating patients with an inherited abnormality of a drug-metabolizing enzyme. The pharmacokinetics of many drugs often exhibit considerable inter-individual variability, largely because of variations in the expression of different CYP enzymes in the liver and other tissues. Relatively selective in vivo substrate probes have been discovered for several major CYP isoforms involved in oxidative drug metabolism. In view of the remarkable progress in this particular field, it is to be expected that more genetic polymorphisms will be reported with the discovery of more and more new drugs in the near future. [ABSTRACT FROM AUTHOR] |
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