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

被引:58
作者
LLERENA, A
HERRAIZ, AG
COBALEDA, J
JOHANSSON, I
DAHL, ML
机构
[1] KAROLINSKA INST,HUDDINGE UNIV HOSP,DEPT CLIN PHARMACOL,S-14186 HUDDINGE,SWEDEN
[2] PSYCHIAT HOSP ADOLFO DIAZ AMBRONA,MERIDA,SPAIN
[3] KAROLINSKA INST,DEPT PHYSIOL CHEM,S-10401 STOCKHOLM 60,SWEDEN
关键词
D O I
10.1038/clpt.1993.197
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. CUPSILONP2D6 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, CUPSILON2D6 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.
引用
收藏
页码:606 / 611
页数:6
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