Semi-quantitative CYP2D6 gene doses in relation to metabolic ratios of psychotropics.
OBJECTIVE
Genetic polymorphisms in cytochrome P450 (CYP) enzyme CYP2D6 have a substantial effect on the success of pharmacotherapy. Different models, including a predicted-phenotype model and a semi-quantitative gene dose (SGD) model, have been developed based on CYP genotype. The objective of this study was to investigate the surplus value of the SGD model in predicting the metabolic ratios (MRs) of the psychotropics venlafaxine, fluoxetine and risperidone.


METHODS
Phenotype prediction and semi-quantitative gene doses were conducted after genotyping for CYP2D6 *3, *4, *5, *6, *9, *10, *41 and gene multiplication.


RESULTS
The predicted-phenotype and SGD model showed increasing mean MRs with increasing predicted metabolic activity and decreasing SGD values, respectively, for all three psychotropics. The reliability of MR prediction was higher for the SGD model.


CONCLUSIONS
Both models are suitable for venlafaxine, fluoxetine and risperidone. In this study, a surplus value of semi-quantitative gene dose model was present, but small, for all three psychotropics.
Department of Clinical Chemistry, St Jansdal Hospital, Harderwijk, The Netherlands.
John W J
JW
Hinrichs
Harriët M
HM
Loovers
Bart
B
Scholten
Jan
J
van der Weide
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D003511:Cyclohexanols / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005473:Fluoxetine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D018628:Gene Dosage; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D010641:Phenotype; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011619:Psychotropic Drugs / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D018967:Risperidone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D003511:Cyclohexanols; D011619:Psychotropic Drugs; D005473:Fluoxetine; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone