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Debrisoquin and mephenytoin hydroxylation phenotypes and CYP2D6 genotype in patients treated with neuroleptic and antidepressant agents

Abstract:

Debrisoquin and S‐mephenytoin hydroxylation phenotypes were determined in 72 Spanish psychiatric patients treated with neuroleptic or antidepressant agents. One patient (1.4%) was classified as a poor metabolizer of S‐mephenytoin. Between both neuroleptic‐ and antidepressant‐treated patients, the distribution of the debrisoquin metabolic ratio was shifted toward higher values compared with 54 drug‐free healthy subjects. Forty percent of patients treated with neuroleptics and 5% of patients treated with antidepressants were classified as poor metabolizers of debrisoquin. CYP2D6 genotype analysis in 36 neuroleptic‐treated patients confirmed that the high metabolic ratios were attributable to inhibition of CYP2D6 and not to overrepresentation of subjects with poor metabolizer genotypes. In 48 selected Spanish drug‐free subjects, CYP2D6 genotype pbkp_redicted the phenotype with 95% accuracy. Neuroleptics and antidepressants interfere at therapeutic doses with phenotyping for CYP2D6 but not for S‐mephenytoin hydroxylation capacity. In psychotropic‐treated patients, genotyping provides a valuable tool for pbkp_rediction of the CYP2D6 phenotype. Clinical Pharmacology and Therapeutics (1993) 54, 606–611; doi: © 1993 American Society for Clinical Pharmacology and Therapeutics