title: Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men.
abstract: OBJECTIVE
  To examine the effect of grapefruit juice on the metabolism of felodipine following intravenous and oral administration.
  
  
  METHODS
  The study had a randomised, four-way, crossover design in 12 healthy males. Single doses of felodipine were given as an intravenous infusion for 1 h (1.5 mg) or as an oral extended release (ER) tablet (10 mg). Grapefruit juice (150 ml) or water was ingested 15 min prior to drug intake.
  
  
  RESULTS
  Intake of grapefruit juice did not significantly alter the intravenous pharmacokinetics of felodipine compared to control treatment, whereas after oral drug administration it did lead to an increase in the mean AUC and Cmax by 72% and 173%, respectively, and the mean absolute bioavailability was increased by 112%. The fraction of the oral felodipine dose reaching the portal system was increased from 45% to 80% when intake of drug was preceded by grapefruit juice ingestion. The pharmacokinetics of the primary metabolite, dehydrofelodipine, was affected by the intake of juice, resulting in a 46% increase in Cmax. Juice intake immediately before oral felodipine resulted in more pronounced haemodynamic effects of the drug as measured by diastolic blood pressure and heart rate. However, the haemodynamic effects of the intravenous administration were not altered by juice intake. Vascular-related adverse events were reported more frequently when oral drug administration was preceded by juice intake compared with control treatment. Taking grapefruit juice immediately prior to intravenous felodipine administration did not cause any alteration in the adverse event pattern.
  
  
  CONCLUSIONS
  The main acute effect of the grapefruit juice on the plasma concentrations of felodipine is mediated by inhibition of gut wall metabolism.
authors.affiliation: Department of Clinical Research, Ferring AB, MalmöSweden.
authors.forename: J
authors.initials: J
authors.lastname: Lundahl
authors.forename: C G
authors.initials: CG
authors.lastname: Regårdh
authors.forename: B
authors.initials: B
authors.lastname: Edgar
authors.forename: G
authors.initials: G
authors.lastname: Johnsson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001628:Beverages; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002957:Citrus; D018592:Cross-Over Studies; D004347:Drug Interactions; D015736:Felodipine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D014018:Tissue Distribution / Q000187:drug effects; D014867:Water
chemical_list: D002121:Calcium Channel Blockers; D014867:Water; C081790:dehydrofelodipine; D015736:Felodipine