Abstract
We investigated the effect of cytochrome P450 (CYP2D6) genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 47 Japanese male schizophrenic inpatients being treated with HAL. Mutation-specific polymerase chain reaction (PCR) analysis was used to detect CYP2D6*10 as the C188C1T mutation in exon 1. A long-PCR analysis method was used to detect CYP2D6*5. Allele frequencies of CYP2D6*5 and CYP2D6*10 were 4.3% and 34.0%, respectively. Plasma concentrations of HAL and RHAL were measured using high-performance liquid chromatography. The ranges of the plasma concentration of 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, respectively. Plasma RHAL/HAL ratios (R/H ratios) ranged from 0.06 to 1.88 (mean +/- SD, 0.48+/-0.32, n = 47). The analysis was performed among the four genotype groups: CYP2D6*1/CYP2D6*1 (n = 11), CYP2D6*1/CYP2D6*10 (n = 11), CYP2D6*10/CYP2D6*10 (n = 6) and those who have CYP2D6*5 allele (CYP2D6*1/ CYP2D6*5 or CYP2D6*5/CYP2D6*10 (n = 4). We observed significant tendency in effects of CYP2D6 genotypes on plasma concentration of HAL and significant effects on plasma concentration of RHAL, and R/H ratio. These results we obtained suggested that the plasma concentration of HAL and RHAL were determined partly by CYP2D6 polymorphic activity.
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