| Abstract |
Abstract
Background: Quetiapine (QTP) is an atypical antipsychotic drug. CYP3A4/5 is the main enzyme that metabolizes QTP to N-desalkylquetiapine, an active metabolite. CYP3A5*3 was a common non-functional variant and caused the decrease of function in CYP3A5 activity. CYP3A5 mutant allele may affect the plasma concentration of QTP and treatment outcomes. Moreover, the prevalence of polymorphism of CYP3A5 was different between Asians and Caucasians.
Purpose: This study investigated the effect of CYP3A5 polymorphism on quetiapine concentration in Thai psychiatric patients.
Method: Fifty-three patients receiving QTP at the psychiatric outpatient department of Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand, were enrolled in this study. The plasma concentration of QTP at steady state was measured using the LC-MS/MS method. Patients were genotyped of CYP3A5*3 using a real-time PCR technique with a specific TaqMan® probe and primer.
Results: Thirty-seven (69.81%) patients were female. The prevalence of CYP3A5*1/*1, CYP3A5*1/*3, and CYP3A5*3/*3 were 11.32%, 41.51%, and 47.17%, respectively. The patients who carried CYP3A5*3/*3 had 4.3-fold higher mean plasma concentrations of the QTP than CYP3A5* 1/*3 and CYP3A5*1/*1 but no statistical significance difference (84.89 ± 81.94, 49.77 ± 102.32 and 19.87 ± 11.68, respectively, P=0.181). The concentration per dose (C/D) ratio of QTP was 2.3-fold higher in CYP3A5*3/*3 than in wild-type and CYP3A5*1/*3 patients (0.64 ± 0.45 vs 0.28 ± 0.40, P=0.05).
Conclusions: The C/D ratio of QTP for the patients carrying CYP3A5*3/*3 was higher than for wild-type and heterozygous patients. Therefore, homozygous mutant patients may have an increased risk of adverse effects compared to other groups. The investigation of CYP3A5 genotypes may help adjust the dosage of QTP to reduce adverse effects and improve treatment outcomes for psychiatric patients.
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Publication
Journal Publication
ไทย