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 dr ug therapy. Explanations of a patient's nonresponse, or unexpected adv erse reactions to drugs are required. In many instances, a knowledge o f the drug metabolism status of a patient can be helpful in the select ion of a drug and its dosage regimen, and in the prediction of possibl e drug/drug interactions when two or more drugs have to be administere d concomitantly. Important information on these topics may be obtained by phenotyping patients prior to drug therapy. The metabolism of vari ous antidepressant and neuroleptic drugs is catalyzed by CYP2D6, a cyt ochrome 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) a re described, and substrates identified. Phenotyping of patients for C YP2D6 activity and mephenytoin hydroxylase activity is described.