DEBRISOQUIN AND MEPHENYTOIN HYDROXYLATION PHENOTYPES AND CYP2D6 GENOTYPE IN PATIENTS TREATED WITH NEUROLEPTIC AND ANTIDEPRESSANT AGENTS

Debrisoquin and S-mephenytoin hydroxylation phenotypes were determined in 72 Spanish psychiatric patients treated with neuroleptic or antide pressant agents. One patient (1.4%) was classified as a poor metaboliz er of S-mephenytoin. Between both neuroleptic- and antidepressant-trea ted patients, the distribution of the debrisoquin metabolic ratio was shifted toward higher values compared with 54 drug-free healthy subjec ts. Forty percent of patients treated with neuroleptics and 5% of pati ents treated with antidepressants were classified as poor metabolizers of debrisoquin. CUPSILONP2D6 genotype analysis in 36 neuroleptic-trea ted patients confirmed that the high metabolic ratios were attributabl e to inhibition of CYP2D6 and not to overrepresentation of subjects wi th poor metabolizer genotypes. In 48 selected Spanish drug-free subjec ts, CUPSILON2D6 genotype predicted the phenotype with 95% accuracy. Ne uroleptics and antidepressants interfere at therapeutic doses with phe notyping for CYP2D6 but not for S-mephenytoin hydroxylation capacity. In psychotropic-treated patients, genotyping provides a valuable tool for prediction of the CYP2D6 phenotype.