title: Association between PK/PD-involved gene polymorphisms and carbamazepine-individualized therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  SCN1A IVS5-91G>A gene polymorphism is potential genetic biomarker associated with the PK of CBZ.
authors: Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
authors: Chun-Lai
authors: CL
authors: Ma
authors: Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
authors: Zheng
authors: Z
authors: Jiao
authors: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors: Xun-Yi
authors: XY
authors: Wu
authors: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
authors: Zhen
authors: Z
authors: Hong
authors: Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
authors: Zhi-Yuan
authors: ZY
authors: Wu
authors: Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
authors: Ming-Kang
authors: MK
authors: Zhong
mesh_terms: D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy / Q000453:epidemiology; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D057285:Precision Medicine; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D051544:Cytochrome P-450 CYP3A; D004851:Epoxide Hydrolases; D014453:Glucuronosyltransferase; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D062550:NAV1.1 Voltage-Gated Sodium Channel; C000715087:ABCC2 protein, human; C568242:SCN1A protein, human; C510163:CYP3A4 protein, human; C491474:UGT2B7 protein, human; C522330:EPHX1 protein, human
keywords: ABCC2; EPHX1; SCN1A; carbamazepine; carbamazepine 10,11-epoxide; epilepsy; genetic polymorphisms