Inhibition of cytochrome P450 by furanocoumarins in grapefruit juice and herbal medicines

Acta Pharmacol Sin. 2004 Feb;25(2):129-36.

Abstract

Furanocoumarins (psoralens) exist in various plants and some of them are used to cure skin diseases. These chemicals draw attentions recently because of their abilities to arouse drug interaction through inhibition of cytochrome P450. Grapefruit juice is a well-known example for food-drug interaction. But in vitro and in vivo studies have shown that the causative components are mainly furanocoumarin derivatives with geranyloxy side chains. In vitro experiments confirmed that furanocoumarins from grapefruit juice are both competitive and mechanism-based inhibitors of CYP3A4. Although the inhibition appeared to be stronger in the dimers than that in the monomers, all contribute comprehensively to the grapefruit juice-drug interaction. Further experiments with other furanocoumarins and related citrus fruits or umbelliferous herbal medicines indicate that drug interaction might also occur with stuffs other than grapefruit juice, especially with traditional medicine.

Publication types

  • Review

MeSH terms

  • Animals
  • Beverages* / analysis
  • Citrus* / chemistry
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drugs, Chinese Herbal / pharmacology*
  • Furocoumarins / isolation & purification
  • Furocoumarins / pharmacology*
  • Humans
  • Microsomes, Liver / metabolism
  • Plants, Medicinal / chemistry

Substances

  • Drugs, Chinese Herbal
  • Furocoumarins
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human