[CYP2D6-, CYP2C9- and CYP2C19-based dose adjustments: when do they make sense?].
The efficacy of a drug therapy is influenced by many different factors such as age, weight, comorbidity and co-medication, which vary between patients, as well as fixed parameters such as gender and pharmacogenetic characteristics. Many enzymes involved in drug metabolism are genetically polymorphic, which means that their activity differs depending on a certain genotype. Drugs will be metabolized slowly in individuals who are carriers of a genetic polymorphism, leading to absent or decreased enzyme activity, and these individuals are at particular risk for adverse drug reactions or therapeutic failure. On the other hand, drug therapy could be ineffective if the drug is metabolized too fast because of a genetic polymorphism. The knowledge of these polymorphisms before beginning a drug therapy could help in choosing the right drug in a safe dosage. In particular, three polymorphic drug metabolizing enzymes are responsible for the metabolism of many commonly used drugs. These enzymes, belonging to the cytochrome P450 (CYP) family, are CYP2D6, CYP2C9 and CYP2C19. Besides beta-blockers and antidepressants, several drugs used in cancer therapy, as well as PPIs, NSAIDs, vitamin K-antagonists and oral antidiabetics are metabolized via these enzymes. Especially for drugs with a narrow therapeutic index and a high risk for the development of adverse drug effects, genotyping could be helpful when choosing the right drug in the optimal dosage for individual patients.
Institut für Naturheilkunde und Klinische Pharmakologie, Universität Ulm, Helmholtzstrasse 20, 89081 Ulm, Deutschland.
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Seeringer
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Kirchheiner
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004334:Drug Administration Schedule; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic
C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6