Genetic association between cytochrome P-450 2D6 gene polymorphism and plasma concentration of haloperidol in Japanese schizophrenics.
Haloperidol is one of the major neuroleptics partly metabolized by cytochrome P-450 2D6 (CYP2D6), which has over 10 genetic polymorphisms. The purpose of this study was to investigate whether individual haloperidol plasma concentration was affected by CYP 2D6 gene polymorphisms. The genomic DNA of 56 subjects who have been taking haloperidol were analysed by restriction fragment length polymorphism (RFLP) method to detect the major Caucasian mutations, CYP 2D6A, 2D6B, and the major oriental population mutation, 2D6J. We found 10 cases of the CYP 2D6J mutation, only one case of the CYP 2D6B mutation, and no cases of the CYP 2D6A mutation in the present subjects. Contrary to expectations, haloperidol plasma concentration of the CYP 2D6B mutation case showed a lower haloperidol plasma concentration than the mean value of that of wild type homozygous cases. Haloperidol plasma concentration of 10 subjects who had the CYP 2D6J mutation cases showed no significant difference from that of the wild type homozygous group. These results suggest that the major genetic polymorphisms of CYP 2D6 do not seem to be one of the factors which affect individual haloperidol plasma concentration in Japanese schizophrenics.
Shibata
N
N
Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
Ohnuma
T
T
Baba
H
H
Shimada
H
H
Takahashi
T
T
Arai
H
H
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000097:blood; D005091:Exons; D005260:Female; D006220:Haloperidol / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; D004247:DNA; D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol