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

Authors

  • Wang Ping Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China.
  • Yin Tao Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China.
  • Ma HongYing Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China.
  • Liu DanQi Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China. School of Pharmacy, Central South University, Changsha, Hunan, China.
  • Sheng Yanghao Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China. School of Pharmacy, Central South University, Changsha, Hunan, China.
  • Zhou BoTing Department of Pharmacy, Xiangya Hospital, Central South University, Changsha Hunan, China. School of Pharmacy, Central South University, Changsha, Hunan, China.

DOI:

https://doi.org/10.18433/J37S4K

Abstract

Purpose: 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. Conclusion: 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.

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Published

2015-07-30

How to Cite

Ping, W., Tao, Y., HongYing, M., DanQi, L., Yanghao, S., & BoTing, Z. (2015). 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. Journal of Pharmacy & Pharmaceutical Sciences, 18(3), 256–285. https://doi.org/10.18433/J37S4K

Issue

Vol. 18 No. 3 (2015)

Section

Pharmaceutical Sciences; Review Articles

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