Effects of age and the CYP2D6*10 allele on the plasma haloperidol concentration/dose ratio

The authors studied the effect of aging and the CYP2D6*10 polymorphism on the plasma haloperidol (HAL) concentration after chronic administration of HAL. Subjects were 110 Japanese patients (66 male) treated orally with HAL. Venous blood was obtained from each patient for determination of the HAL concentration/dose (C/D) ratio (the plasma concentration of HAL divided by the daily dose of HAL per kilogram body weight) and for CYP2D6 genotyping. Overall, there was a significant linear correlation between the HAL C/D ratio and age. In subgroup analyses, the correlation was significant for patients with non-2D6*10 homozygous genotypes, but not for those with the 2D6*10 homozygous genotype. Overall, the HAL C/D ratio was significantly higher in older subjects (at least 50 years old) than younger ones (less than 50 years old). The ratio was significantly higher in older than in younger subjects for patients with non-2D6*10 homozygous genotypes, but not for those with the 2D6*10 homozygous genotype. Our results indicate that the effect of age on the HAL C/D ratio depends upon the CYP2D6*10 genotype. Because there are racial differences in the CYP2D6 genotype, further studies should investigate age effects on the HAL C/D ratio in different patient populations.