title: Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
abstract: OBJECTIVE
  To evaluate the effect of regular-strength grapefruit juice, a cytochrome P4503A4 (CYP3A4) inhibitor, on the pharmacokinetics of a commonly prescribed regimen of oral lovastatin.
  
  
  METHODS
  In a randomized crossover study, 16 healthy subjects received a single 40 mg dose of lovastatin in the evening after each consumed an 8-ounce glass of regular-strength grapefruit juice or water with breakfast for 3 consecutive days. The effect of the same grapefruit juice and water regimen on the pharmacokinetics of midazolam (2 mg oral dose given 1 hour after the third day of grapefruit juice and water) was used as a positive control in the same subjects. Plasma concentrations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were determined by an enzyme inhibition assay, and concentrations of lovastatin, lovastatin acid, and midazolam were determined by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  The area under the plasma concentration-time profiles (AUC) and maximum plasma concentrations (Cmax) of HMG-CoA reductase inhibitors increased slightly (-30% for each) after consumption of grapefruit juice. Similar effects on AUC and Cmax (approximately 40% increase for each) were noted after analysis of samples of hydrolyzed plasma (which converts inactive lactones to active hydroxy acid species). The AUC and Cmax values for lovastatin approximately doubled in the presence of grapefruit juice, whereas the same parameters for lovastatin acid increased 1.6-fold. Grapefruit juice caused the AUC for midazolam to increase by a factor of approximately 2.4.
  
  
  CONCLUSIONS
  Daily consumption of a glass of regular-strength grapefruit juice has a minimal effect on plasma concentrations of HMG-CoA reductase inhibitors (approximately 30% to 40% increase) after a 40 mg evening dose of lovastatin.
authors.affiliation: Merck Research Labs, West Point, PA 19486, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Rogers
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: R D
authors.initials: RD
authors.lastname: Amin
authors.forename: K D
authors.initials: KD
authors.lastname: Gagliano
authors.forename: A G
authors.initials: AG
authors.lastname: Porras
authors.forename: R A
authors.initials: RA
authors.lastname: Blum
authors.forename: M F
authors.initials: MF
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: Stepanavage
authors.forename: J M
authors.initials: JM
authors.lastname: Vega
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000097:blood*; D019540:Area Under Curve; D001628:Beverages; D002957:Citrus; D018592:Cross-Over Studies; D018565:Food-Drug Interactions; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000097:blood*; D008148:Lovastatin / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D012016:Reference Values
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin