title: Major determinant factors of the extent of interaction between grapefruit juice and calcium channel antagonists.
abstract: OBJECTIVE
  To evaluate quantitatively the influence of bioavailability and plasma unbound fraction (f(u)) on the extent of interaction between grapefruit juice (GFJ) and calcium antagonists.
  
  
  METHODS
  The extent of drug-GFJ interaction was evaluated from reported clinical interaction studies of 11 calcium antagonists. The relationship between extent of interaction and bioavailability or f(u) was analysed.
  
  
  RESULTS
  The following significant hyperbolic relationships were observed: [Extent] = 12.2/[bioavailability] + 1 and [Extent] = 0.718/[f(u)] + 1.
  
  
  CONCLUSIONS
  Bioavailability and f(u) are major determinant factors of calcium antagonist-GFJ interaction: a drug with smaller bioavailability or lower f(u) is likely to exhibit a more potent interaction, and vice versa.
authors.affiliation: Biostatistics Department, Shionohi and Co., Ltd, Osaka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohnishi
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Ohtani
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sawada
mesh_terms: D019540:Area Under Curve; D001628:Beverages; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D032083:Citrus paradisi / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans
chemical_list: D001798:Blood Proteins; D002121:Calcium Channel Blockers