title: First Analysis of the Association Between CYP3A4/5, ABCB1 Genetic Polymorphisms and Oxcarbazepine Metabolism and Transport in Chinese Epileptic Patients with Oxcarbazepine Monotherapy and Bitherapy.
abstract: OBJECTIVE
  Oxcarbazepine (OXC) is widely used in anti-epileptic treatment. Cytochrome P450 3A4 (CYP3A4), cytochrome P450 3A5(CYP3A5), and ATP-binding cassette sub-family B member 1 (ABCB1) are potential genes involved in OXC metabolisms and transport in vivo. This study aims to examine the genetic effects of CYP3A4, CYP3A5, and ABCB1 on OXC metabolism and transport in Chinese epileptic patients using OXC as monotherapy and bitherapy with lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA).
  
  
  METHODS
  Sixty-six Chinese epileptic patients were recruited from Xiangya Hospital Central South University, of whom 40 patients were receiving OXC monotherapy, 11 patients were placed in the OXC bitherapy group combined with one enzyme-inducing anti-epileptic drugs (LTG or LEV), and 15 patients were placed in the OXC bitherapy group combined with VPA. Oxcarbazepine and its main metabolite 10-hydrocarbazepine (MHD) plasma concentrations were measured using high performance liquid chromatography (HPLC)-UV method. In addition, eight single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, ABCB1 gene were genotyped by polymerase chain reaction-improved multiple ligase detection reaction (PCR-iMLDR).
  
  
  RESULTS
  In the OXC+VPA group, ABCB1 rs2032582 and rs2032582-rs10234411-rs1045642 TAG haplotype were associated with MHD and MHD+OXC plasma concentration before permutation test. In OXC monotherapy and OXC+ LTG/LEV groups, no significant association between genetic polymorphisms in CYP3A4/5, ABCB1 gene and OXC plasma concentration parameters were observed.
  
  
  CONCLUSIONS
  CYP3A4/5 and ABCB1 genetic variants might not take part in the metabolism and transport of MHD and OXC among epileptic patients using OXC monotherapy and bitherapy in combination with LEV, LTG or VPA.
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Hong-ying
authors.initials: HY
authors.lastname: Ma
authors.forename: Dan-Qi
authors.initials: DQ
authors.lastname: Liu
authors.forename: Yangh-ao
authors.initials: YA
authors.lastname: Sheng
authors.forename: Bo-Ting
authors.initials: BT
authors.lastname: Zhou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage; D044466:Asian People / Q000235:genetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000927:Anticonvulsants; D002220:Carbamazepine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000078330:Oxcarbazepine