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Debrisoquin and mephenytoin hydroxylation phenotypes and CYP2D6 genotype in patients treated with neuroleptic and antidepressant agents
Author(s) -
LLerena Adrián,
Herraíz Angustias G,
Cobaleda Jesús,
Johansson Inger,
Dahl MarjaLiisa
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.197
Subject(s) - mephenytoin , cyp2d6 , antidepressant , genotype , pharmacology , pharmacogenetics , medicine , hydroxylation , psychiatry , biology , genetics , enzyme , biochemistry , gene , anxiety
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. Clinical Pharmacology and Therapeutics (1993) 54 , 606–611; doi: 10.1038/clpt.1993.197