Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers.

Article Details

Citation

Copy to clipboard

Kim KA, Joo HJ, Lee HM, Park JY

Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers.

Pharmacogenet Genomics. 2014 Jan;24(1):35-42. doi: 10.1097/FPC.0000000000000020.

PubMed ID

24240480 [ View in PubMed

]

Abstract

BACKGROUND AND OBJECTIVES: Quetiapine is an atypical antipsychotic drug used to treat schizophrenia and acute episodes of mania. Quetiapine is metabolized by CYP3A enzymes including CYP3A5 and is a substrate of P-glycoprotein, an efflux drug transporter encoded by the ABCB1 gene. We assessed the effects of ABCB1 [c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), c.3435C>T (rs1045642)] and CYP3A5*3 (6986A>G) (rs776746) polymorphisms on the pharmacokinetics of quetiapine in humans. MATERIALS AND METHODS: Forty healthy male individuals were enrolled, and their ABCB1 and CYP3A5 polymorphisms were assessed. After a single dose of 100 mg quetiapine was administered, plasma concentrations of quetiapine were measured for 24 h and pharmacokinetic analysis was carried out. RESULTS: The ABCB1 polymorphisms including c.1236C>T, c.2677G>T/A, and c.3435C>>T did not affect plasma levels of quetiapine, and its pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the CYP3A5*3 polymorphism significantly affected the plasma level of quetiapine and its pharmacokinetics. The peak plasma concentration of quetiapine was 208.39 ng/ml for CYP3A5*1/*1, 243.46 ng/ml for CYP3A5*1/*3, and 332.94 ng/ml for CYP3A5*3/*3 (P=0.0118). The mean AUC(inf) (area under the time vs. concentration curve from 0 to infinity) value was 627.3, 712.77, and 1045.29 ng h/ml, respectively (P=0.0017). CONCLUSION: The results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics. These findings suggest that the CYP3A5 genetic polymorphism affects the disposition of quetiapine and provide a plausible explanation for interindividual variation in the disposition of this drug.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Quetiapine	Cytochrome P450 3A5	Protein	Humans	Unknown	Substrate	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Quetiapine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details