Association between PK/PD-involved gene polymorphisms and carbamazepine-individualized therapy. (August 2015)

• Record Type: Journal Article
• Authors: Ma, Chun-Lai; Jiao, Zheng; Wu, Xun-Yi; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang
• Is Part Of: Pharmacogenomics. Volume 16:Number 13(2015)
• Page Start: 1499
• Page End: 1512
• Publication Date: 2015-08
• Subjects: ABCC2 -- carbamazepine -- carbamazepine 10, 11-epoxide -- EPHX1 -- epilepsy -- genetic polymorphisms -- SCN1A; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.15.94
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: To evaluate the association between the major genetic variants involved in the pharmacokinetic/pharmacodynamic (PK/PD) properties of carbamazepine (CBZ) and its maintenance doses and concentrations.Patients & methods: The genotypes of 166 patients receiving CBZ monotherapy were detected using high-resolution melting curve (HRM) and TaqMan methods.Results: Both univariate and multiple regression analyses revealed that carriers of the SCN1A IVS5–91G>A or EPHX1 c.337T>C allele tended to require a higher CBZ dose and a lower CBZ natural logarithmic concentration–dose ratio (lnCDR) than noncarriers (p < 0.05). Furthermore, two interactions between these genes were associated with the lnCDR and the maintenance dosage of CBZ, respectively.Conclusion: SCN1A IVS5–91G>A gene polymorphism is potential genetic biomarker associated with the PK of CBZ.