Effects of smoking and cytochrome P450 2D6*10 allele on the plasma haloperidol concentration/dose ratio.
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.


CONCLUSIONS
Our results suggest that the effect of smoking on the HAL C/D ratio depends on the CYP2D6*10 genotype.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000704:Analysis of Variance; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D008875:Middle Aged; D012907:Smoking / Q000097:blood* / Q000235:genetics*
D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol