A new herb-drug interaction of Polygonum cuspidatum, a resveratrol-rich nutraceutical, with carbamazepine in rats

Ying Chang Chi, Shiuan Pey Lin, Yu Chi Hou*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

39 Scopus citations

Abstract

Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE), an active metabolite. This study investigated the acute and chronic effects of Polygonum cuspidatum (PC), a resveratrol-rich nutraceutical, on the pharmacokinetics of CBZ in rats and the underlying mechanisms. Rats were orally administered CBZ (200mg/kg) alone and coadministered with a single dose and the 7th dose of PC (2g/kg) in a crossover design. The concentrations of CBZ and CBZE in serum and various tissues were determined by HPLC method. The results showed that PC significantly increased the AUC 0-t of CBZ and CBZE, whereas the formation rate of CBZE was decreased. Tissue analysis showed that the concentrations of CBZ and CBZE in brain, liver and kidney were significantly increased by PC. Cell studies indicated that the efflux function of MRP 2 was inhibited by the serum metabolites of PC. In conclusion, PC markedly increased the systemic exposure and brain concentration of CBZ and CBZE through inhibiting the activities of CYP 3A and MRP 2.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalToxicology and Applied Pharmacology
Volume263
Issue number3
DOIs
StatePublished - 15 09 2012
Externally publishedYes

Keywords

  • CYP 3A
  • Carbamazepine
  • Carbamazepine-10,11-epoxide
  • Herbal-drug interaction
  • MRP 2
  • Polygonum cuspidatum

Fingerprint

Dive into the research topics of 'A new herb-drug interaction of Polygonum cuspidatum, a resveratrol-rich nutraceutical, with carbamazepine in rats'. Together they form a unique fingerprint.

Cite this