| Abstract |
Abstract
Background
Quetiapine (QTP) has been widely used for the treatment of psychiatric problems in patients. QTP is metabolized primarily by CYP3A4/5 enzymes. Moreover, CYP2D6 also plays a minor role in QTP metabolism. Therefore, the inter-individual variation of CYP3A4/5 and CYP2D6 function may affect QTP plasma concentration and treatment outcomes. Previously reported genetic polymorphisms of CYP3A4/5 and CYP2D6 genes affect the enzyme functions. CYP3A4*22 was not found in Thais. However, CYP3A5*3 was the most common non-functional variant and caused loss of CYP3A5 activity. CYP3A5*3 and CYP2D6*10 were common mutant alleles in the Thai population.
Keywords: Psychiatric Patients, Quetiapine, Plasma level, CYP3A5 Polymorphisms, CYP2D6 Polymorphisms
Purpose
This study aimed to investigate the correlation between the genetic variation of CYP3A5 and CYP2D6 and QTP plasma levels in Thai psychiatric patients.
Method
Thirty-eight psychiatric patients who received QTP at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand, were enrolled in this study. QTP blood sample was collected at a steady state. CYP3A5 and CYP2D6 polymorphisms were determined by real-time PCR technique with a specific TaqMan® probe and primer. In addition, QTP blood concentrations were determined by LC-MS/MS method.
Results
Of the 38 psychiatric patients investigated for CYP3A5 polymorphism, only 5 (13.16%) were CYP3A5*1/*1, 15 (39.47%) were CYP3A5*1/*3, and 18 (47.37%) were CYP3A5*3/*3. Prevalence of CYP2D6 polymorphism were CYP2D6*1/*1 4 (10.53%), CYP2D6*1/*10 23 (60.53%), and CYP2D6*10/*10 11 (28.95%). Concentrations per dose (C/D) ratio of QTP was 2 times higher in CYP3A5*3/*3 than wide-type and heterozygous patients (1.58±2.78, 0.64±0.61, 0.50±0.59, respectively) (P=0.276). Moreover, The C/D ratio of QTP for the patients carrying CYP2D6*10/*10 was higher than wide-type and heterozygous patients but had no statistical significance (1.49±3.04, 0.81±1.00, 0.85±1.49, respectively) (P=0.674).
Discussion and Conclusions
CYP3A5 and CYP2D6 heterozygous mutants had higher C/D ratios of QTP than wide-type but no statistical significance because of the low sample size. Therefore, CYP3A5 and CYP2D6 genotypes may need to be investigated to adjust the QTP dose regimen for psychiatric patients to reduce adverse effects and improve clinical outcomes.
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Publication
Journal Publication
ไทย