Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid

Clin Pharmacol Ther. 1998 Apr;63(4):397-402. doi: 10.1016/S0009-9236(98)90034-0.


Background: Grapefruit juice increases the bioavailability of several drugs known to be metabolized by CYP3A4. We wanted to investigate a possible interaction of grapefruit juice with lovastatin, a cholesterol-lowering agent that is partially metabolized by CY P3A4.

Methods: An open, randomized, two-phase crossover study with an interval of 2 weeks between the phases was carried out. Ten healthy volunteers took either 200 ml double-strength grapefruit juice or water orally three times a day for 2 days. On day 3, each subject ingested 80 mg lovastatin with either 200 ml grapefruit juice or water, and an additional dose of 200 ml was ingested 1/2 and 1 1/2 hours after lovastatin intake. Serum concentrations of lovastatin and lovastatin acid were measured up to 12 hours.

Results: Grapefruit juice greatly increased the serum concentrations of both lovastatin and lovastatin acid. The mean peak serum concentration (Cmax) of lovastatin was increased about 12-fold (range, 5.2-fold to 19.7-fold; p < 0.001) and the area under the concentration-time curve [AUC(0-12)] was increased 15-fold (range, 5.7-fold to 26.3-fold; p < 0.001) by grapefruit juice. The mean Cmax and AUC(0-12) of lovastatin acid were increased about fourfold (range, 1.8-fold to 11.5-fold; p < 0.001) and fivefold (range, 2.4-fold to 23.3-fold; p < 0.001) by grapefruit juice, respectively. The half-lives of lovastatin and lovastatin acid remained unchanged.

Conclusions: Grapefruit juice can greatly increase serum concentrations of lovastatin and its active metabolite, lovastatin acid, probably by preventing CYP3A4-mediated first-pass metabolism in the small intestine. The concomitant use of grapefruit juice with lovastatin and simvastatin should be avoided, or the dose of these 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors should be reduced accordingly.

Publication types

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

MeSH terms

  • Acids / blood
  • Adult
  • Area Under Curve
  • Beverages*
  • Citrus*
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Food-Drug Interactions
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood*
  • Lovastatin / blood*
  • Male
  • Mixed Function Oxygenases / metabolism
  • Reference Values


  • Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cytochrome P-450 Enzyme System
  • Lovastatin
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human