Effects of furanocoumarin derivatives in grapefruit juice on nifedipine pharmacokinetics in rats

Pharm Res. 2001 Feb;18(2):177-82. doi: 10.1023/a:1011028401189.


Purpose: It has been reported that grapefruit juice (GJ) causes a pharmacokinetic interaction with many drugs after co-ingestion. It is postulated that the substances in GJ may inhibit the first-pass metabolism during the intestinal absorption process. In recent years, several furanocoumarin derivatives that inhibit P450 activity in intestinal microsomes were isolated from GJ. In this study, we report the effects of the furanocoumarin derivatives in GJ on the nifedipine (NFP) pharmacokinetics in rats.

Methods: Three furanocoumarin derivatives (bergaptol [BT], bergamottin [BG], and 6',7'-dihydroxybergamottin [DHB]) found in GJ were used in this study. Each furanocoumarin was reconstituted in orange juice at the same concentration as in the GJ. Two milliliters of each sample was administered into the rat duodenum. After 30 min, NFP was intraduodenally administered at a dose of 3 mg/kg body weight. The NFP concentrations in the plasma samples were determined by HPLC.

Results: A significant increase in the AUC of NFP was observed only in the rats administered BG; 1.5 times that of the control group. The result was quite identical with that of the group that was administered GJ. BT and DHB had no significant effects on the NFP pharmacokinetics.

Conclusions: The results strongly suggested that BG in GJ might be the substance that elevates the NFP plasma concentrations.

MeSH terms

  • Animals
  • Area Under Curve
  • Calcium Channel Blockers / pharmacokinetics*
  • Citrus / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Food-Drug Interactions / physiology*
  • Furocoumarins / pharmacology
  • Male
  • Nifedipine / pharmacokinetics*
  • Rats
  • Rats, Wistar


  • Calcium Channel Blockers
  • Furocoumarins
  • Nifedipine
  • bergamottin
  • bergaptol
  • 6',7'-dihydroxybergamottin