Grapefruit juice--felodipine interaction in the elderly

Clin Pharmacol Ther. 2000 Jul;68(1):28-34. doi: 10.1067/mcp.2000.107524.


Background: Grapefruit juice can increase the oral bioavailability of a broad range of medications. This interaction has not been assessed in the elderly.

Methods: Twelve healthy elderly people (70 to 83 years of age) were administered 5 mg felodipine extended release with 250 mL grapefruit juice or water in a single-dose study. Subsequently, 6 of these people received 2.5 mg felodipine for 2 days, followed by 5 mg felodipine for 6 days with 250 mL grapefruit juice or water in a steady-state study. Plasma concentrations of felodipine and dehydrofelodipine metabolite, blood pressure, and heart rate were measured over 24 hours after single and final steady-state dose.

Results: Mean felodipine area under the curve and maximum concentration were 2.9-fold and 4.0-fold greater, respectively, with grapefruit juice in both studies. Interindividual variability in the extent of the interaction was high. Felodipine apparent elimination half-life was not altered. Dehydrofelodipine area under the curve and maximum concentration were increased and dehydrofelodipine/felodipine area under the curve ratio was reduced. Systolic and diastolic blood pressures were lower with grapefruit juice in the single-dose study, whereas they were not different between treatments in the steady-state study. Curvilinear relationships existed between plasma felodipine concentration and changes in systolic and diastolic blood pressures. Heart rates were higher with grapefruit juice in both studies; however, this effect was greater and more prolonged at steady state.

Conclusions: A normal dietary amount of grapefruit juice produced a pronounced, unpredictable, and sustained pharmacokinetic interaction with felodipine by reducing its presystemic metabolism in the elderly. The different blood pressure results between the studies can be explained by felodipine concentration-blood pressure response relationships. The elderly should be particularly cautioned about concomitant grapefruit juice and felodipine ingestion.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / blood
  • Antihypertensive Agents / pharmacology*
  • Area Under Curve
  • Beverages
  • Blood Pressure / drug effects*
  • Citrus*
  • Diastole / drug effects
  • Felodipine / administration & dosage
  • Felodipine / analogs & derivatives*
  • Felodipine / blood
  • Felodipine / pharmacology*
  • Female
  • Food-Drug Interactions
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Male
  • Posture
  • Reference Values
  • Systole / drug effects
  • Time Factors


  • Antihypertensive Agents
  • dehydrofelodipine
  • Felodipine