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 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 predicted 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 prediction of the CYP2D6 phenotype.
LLerena
A
A
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Herraíz
A G
AG
Cobaleda
J
J
Johansson
I
I
Dahl
M L
ML
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D003647:Debrisoquin / Q000493:pharmacokinetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008617:Mephenytoin / Q000493:pharmacokinetics*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D008617:Mephenytoin; D003647:Debrisoquin