Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance

Eur J Clin Pharmacol. 1992;42(3):313-7. doi: 10.1007/BF00266354.

Abstract

The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1, and in the AUC from 23 to 65 nmol.h.l-1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (-9%) than did water (0%).

MeSH terms

  • Adult
  • Analysis of Variance
  • Beverages*
  • Blood Pressure / drug effects
  • Citrus*
  • Felodipine / pharmacokinetics*
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged

Substances

  • Felodipine