RESUMO
OBJECTIVE: This study was carried out to evaluate the influence of CYP2D6 polymorphism and smoking on the plasma clearance of haloperidol (HAL) levels, accounting for the antipsychotic dose, body weight, and coadministration of other drugs. METHODS: Subjects were 110 Japanese patients (66 male, 44 female) diagnosed with schizophrenia, dementia, or mood disorder and treated orally with HAL. Venous blood was obtained from each patient to determine the HAL concentration/dose (C/D) ratio (plasma concentration of HAL divided by the daily dose of HAL per body weight) and for CYP2D6 genotyping. RESULTS: There was no significant difference in the HAL C/D ratio between nonsmokers and smokers. In patients with a non-2D6*10 homozygous genotype, smokers had a significantly lower HAL C/D ratio than nonsmokers, whereas smokers with a 2D6*10 homozygous genotype had a significantly higher HAL C/D ratio than those with a non-2D6*10 homozygous genotype. CONCLUSION: Our results suggest that the effect of smoking on the HAL C/D ratio depends on the CYP2D6*10 genotype.
Assuntos
Alelos , Citocromo P-450 CYP2D6/genética , Haloperidol/sangue , Fumar/sangue , Fumar/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Relação Dose-Resposta a Droga , Feminino , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/enzimologia , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Alelos , Citocromo P-450 CYP2D6/genética , Haloperidol/administração & dosagem , Haloperidol/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Pessoa de Meia-Idade , Estatísticas não ParamétricasRESUMO
OBJECTIVE: The purpose of the present study was to investigate whether plasma fluvoxamine (FV) concentration is associated with CYP2D6*10 allele polymorphisms. METHODS: Subjects were 46 Japanese patients (21 males) carrying neither *3, *4 nor *5 alleles and treated orally using FV. Venous blood was obtained from each patient for determination of FV concentration/dose (C/D) ratio (plasma concentration of FV divided by daily dose of FV per body weight) and CYP2D6 genotyping. RESULTS: No significant differences in FV C/D ratio were found between subjects with no (n=13), one (n=18) or two (n=15) *10 alleles. CONCLUSION: Our results indicate that CYP2D6*10 genotypes do not exert significant effects on FV C/D ratio. As CYP2D6 genotypes differ with ethnic background, further studies should be conducted in different populations.
