The effect of cytochrome P450 2D6 genotypes on haloperidol metabolism: A preliminary study in a psychiatric population

Citation
T. Someya et al., The effect of cytochrome P450 2D6 genotypes on haloperidol metabolism: A preliminary study in a psychiatric population, PSY CLIN N, 53(5), 1999, pp. 593-597
Citations number
27
Categorie Soggetti
Clinical Psycology & Psychiatry
Journal title
PSYCHIATRY AND CLINICAL NEUROSCIENCES
ISSN journal
13231316 → ACNP
Volume
53
Issue
5
Year of publication
1999
Pages
593 - 597
Database
ISI
SICI code
1323-1316(199910)53:5<593:TEOCP2>2.0.ZU;2-3
Abstract
We investigated the effect of cytochrome P450 (CYP2D6) genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 47 Japanese m ale schizophrenic inpatients being treated with HAL. Mutation-specific poly merase chain reaction (PCR) analysis was used to detect CYP2D6*10 as the C1 88C1T mutation in exon 1. A long-PCR analysis method was used to detect CYP 2D6*5, Allele frequencies of CYP2D6*5 and CYP2D6*10 were 4.3% and 34.0%, re spectively. Plasma concentrations of HAL and RHAL were measured using high- performance liquid chromatography. The ranges of the plasma concentration o f HAL and RHAL corrected to the dose were 0.28-1.60 (mean +/- SD, 0.66+/-0. 25, n=47) ng/mL/mg and 0.03-3.00 (mean+/-SD, 0.36+/-0.46, n=47) ng/mL, resp ectively. Plasma RHAL/HAL ratios (R/H ratios) ranged from 0.06 to 1.85 (mea n+/-SD, 0.48+/-0.32, n=47). The analysis was performed among the four genot ype groups:CYP2D6*1/CYP206*1 (n=11), CYP2D6*1/CYP2D6*10 (n=11), CYP2D6*10/C YP2D6*10 (n=6) and those who have CYP2D6*5 allele (CYP2D6*1/ CYP2D6*5 or CY P2D6*5/CYP2D6*10 (n=4). We observed significant tendency in effects of CYP2 D6 genotypes on plasma concentration of HAL and significant effects on plas ma concentration of RHAL, and R/H ratio. These results we obtained suggeste d that the plasma concentration of HAL and RHAL were determined partly by C YP2D6 polymorphic activity.