Major determinant factors of the extent of interaction between grapefruit juice and calcium channel antagonists

Aim 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. Conclusion 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.