Polymorphism in the metabolism of drugs, including antidepressant drugs: comments on phenotyping.
In neurochemistry there are advantages in determining how patients are likely to react to psychoactive drugs prior to the commencement of drug therapy. Explanations of a patient's nonresponse, or unexpected adverse reactions to drugs are required. In many instances, a knowledge of the drug metabolism status of a patient can be helpful in the selection of a drug and its dosage regimen, and in the prediction of possible drug/drug interactions when two or more drugs have to be administered concomitantly. Important information on these topics may be obtained by phenotyping patients prior to drug therapy. The metabolism of various antidepressant and neuroleptic drugs is catalyzed by CYP2D6, a cytochrome P450 isozyme (also named P450IID6), whereas the metabolism of other drugs may involve different cytochromes P450. The properties of CYP2D6 and four other isozymes (CYP1A1, CYP1A2, CYP2C8/9 and CYP3A4) are described, and substrates identified. Phenotyping of patients for CYP2D6 activity and mephenytoin hydroxylase activity is described.
Coutts
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RT
Neurochemical Research Unit, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton.
D002997:Clomipramine / Q000378:metabolism* / Q000627:therapeutic use; D003580:Cytochromes / Q000494:pharmacology; D003640:Dealkylation / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy; D003891:Desipramine / Q000378:metabolism* / Q000627:therapeutic use; D003915:Dextromethorphan / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D007099:Imipramine / Q000378:metabolism* / Q000627:therapeutic use; D007527:Isoenzymes / Q000494:pharmacology; D008297:Male; D008617:Mephenytoin / Q000378:metabolism / Q000652:urine; D009661:Nortriptyline / Q000378:metabolism* / Q000627:therapeutic use; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*
D003580:Cytochromes; D007527:Isoenzymes; D003915:Dextromethorphan; D009661:Nortriptyline; D002997:Clomipramine; D007099:Imipramine; D008617:Mephenytoin; D003891:Desipramine