Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol

Citation
Y. Suzuki et al., Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol, THER DRUG M, 23(4), 2001, pp. 363-368
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
THERAPEUTIC DRUG MONITORING
ISSN journal
0163-4356 → ACNP
Volume
23
Issue
4
Year of publication
2001
Pages
363 - 368
Database
ISI
SICI code
0163-4356(200108)23:4<363:IOTCP2>2.0.ZU;2-I
Abstract
The authors studied the interactive effects of the coadministration of halo peridol and chlorpromazine on plasma concentrations of haloperidol and redu ced haloperidol. The subjects were 43 Japanese male schizophrenic inpatient s who were concomitantly treated with chlorpromazine before or after monoth erapy with haloperidol. Coadministration of chlorpromazine produced signifi cant increases in the plasma concentrations of haloperidol (P < 0.01) and r educed haloperidol (P < 0.001) by an average of 28.5% +/- 83.3% and 160.8% +/- 288.9%, respectively. However, there were marked interindividual variat ions in the interactive effects of chlorpromazine. The authors analyzed the importance of five CYP2D6 genotypes, *1/*1, *1/*10, *10/*10, *1/*5, and *5 /*10 on the percentage of change in plasma concentrations of haloperidol an d reduced haloperidol. Patients with the CYP2D6*5 allele (n = 4) showed a s ignificantly smaller increase in plasma concentrations of haloperidol (P < 0.05) and a slightly smaller increase in those of reduced haloperidol (P = 0.074) in response to the coadministration of chlorpromazine compared than those with the CYP2D6*1/*1 genotype (n = 8). Those with the CYP2D6*1/*1 gen otype (n = 8) showed a trend toward greater increases in plasma concentrati ons of haloperidol than those with other genotypes (P = 0.087).