Aim: To evaluate quantitatively the influence of bioavailability and plasma unbound fraction (fu) 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 fu was analysed. Results: The following significant hyperbolic relationships were observed: [Extent] = 12.2/[bioavailability] + 1 and [Extent] = 0.718/[fu ] + 1. Conclusions: Bioavailability and fu are major determinant factors of calcium antagonist-GFJ interaction: a drug with smaller bioavailability or lower fu is likely to exhibit a more potent interaction, and vice versa.
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