Major determinant factors of the extent of interaction between grapefruit juice and calcium channel antagonists.
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.
Ohnishi
Ayako
A
Biostatistics Department, Shionohi and Co., Ltd, Osaka, Japan.
Ohtani
Hisakazu
H
Sawada
Yasufumi
Y
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
D001798:Blood Proteins; D002121:Calcium Channel Blockers