Archives of Pharmacal Research

, Volume 37, Issue 12, pp 1617–1623 | Cite as

Effect of Sophora flavescens on the pharmacokinetics of carbamazepine in rats

  • Lei Shi
  • Xue-Liang Dang
  • Xin-You Liu
  • Hua-Mei Wei
  • Meng-Meng Yang
  • Yan Zhang
Research Article

Abstract

Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A4 which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE). CBZE is an active and toxicity metabolite, and it is a substrate of MRP-2. Using CBZ for a long time can cause hepatic injury. Sophora flavescens (SF) is a medicinal herb used for the protected hepatic injury. This study investigated the acute and chronic effects of SF on the pharmacokinetics of CBZ in rats. The concentrations of CBZ and CBZE in plasma and tissues were determined by HPLC method. The results showed that SF which significantly decreased the AUC0-t of CBZ, increased CBZE conversely. Tissue analysis showed that the concentrations of CBZ and CBZE in brain and liver were decreased by SF. In addition, the distribution of CBZE in kidney was reduced significantly, which influenced the CBZE excretion and increased the drug toxic potentially. Results in the current study suggest that patients using CBZ might be cautioned in the use of SF extract or Sophora-derived products. Meanwhile, patients receiving drugs which are substrates of CYP 3A4 and/or MRP-2 should be advised of the potential herb–drug interaction to reduce the risk of therapeutic failure or increased toxicity of conventional drug therapy.

Keywords

Sophora flavescens Carbamazepine Carbamazepine-10,11-epoxide Pharmacokinetics Herb–drug interaction 

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Copyright information

© The Pharmaceutical Society of Korea 2014

Authors and Affiliations

  • Lei Shi
    • 1
  • Xue-Liang Dang
    • 1
  • Xin-You Liu
    • 1
  • Hua-Mei Wei
    • 1
  • Meng-Meng Yang
    • 1
  • Yan Zhang
    • 1
  1. 1.Department of Pharmacy, Tangdu HospitalFourth Military Medical UniversityXi’anPeople’s Republic of China

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