A CYP2D6 phenotype-genotype mismatch in Japanese psychiatric patients.
The aim of the present study was to seek a CYP2D6 genotypic-phenotypic discordance possibility in Japanese patients under psychotropic drug treatment where the CYP2D6 status and pharmacodynamic responses differ from those in Caucasian psychiatric patients. Ninety drug-free, healthy volunteers and 14 patients undergoing psychotropic drug treatment were phenotyped for their individual CYP2D6 activity using dextromethorphan as a probe, and then the metabolic ratio (MR) was calculated. For the genotyping, eight mutant alleles of the CYP2D6 genes were identified. Serum concentrations of two frequently co-medicated psychotropic drugs, biperiden and levomepromazine, were determined by GC/MS. Genotyping revealed no poor metabolizers (PMs) enrolled in our study. Healthy volunteers exhibited an identical phenotype-genotype concordance, whereas 7 of the 14 patients had significantly high (p < 0.05) MRs compared with genotype-matched volunteers. Three of the patients who had the extensive metabolizer (EM) genotype had extremely high MRs and were classified as phenotypic PMs. Five patients plus all of the seven high MR patients were treated with levomepromazine and/or biperiden, respectively. Their mean serum steady-state concentrations were 27.4 and 7.6 ng/ml, respectively. A CYP2D6 phenotype-genotype mismatch (phenocopying) can occur in Japanese psychiatric patients receiving clinical doses of some psychotropic drugs where the prevalence of PMs is low and the pharmacodynamic responses to those drugs are enhanced compared to Caucasian patients.
Ieiri
I
I
Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Yonago, Japan. ieiri-ttr@umin.ac.jp
Yamada
S
S
Seto
K
K
Morita
T
T
Kaneda
T
T
Mamiya
K
K
Tashiro
N
N
Higuchi
S
S
Otsubo
K
K
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6