Interactions between Grapefruit Juice and Calcium Channel Antagonists

The extent of interaction between calcium channel antagonists and grapefruit juice varies widely among drugs. Coadministration of calcium channel antagonists with grapefruit juice can elevate the bioavailability of drugs and alter pharmacokinetic parameters of the drug. A calcium channel antagonist with lower bioavailability is likely to be more affect-ed by grapefruit juice. The area under the concentration-time curve and peak serum con-centrations of azelnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nisoldipine, nitrendipine and verapamil are influenced by grapefruit juice. Conversely, pharmacokinetic parameters of amlodipine and diltiazem are not affected by grapefruit juice. The action of grapefruit juice is rapid, and a single exposure to one glass of juice can usually produce a significant interaction. Furanocoumarins primarily contribute to grapefruit juice-drug interactions in humans. Cytochrome P4503A4 and P-glycoprotein may act in tandem as a barrier to oral delivery of drugs. The main mechanism for en-hanced bioavailability of drugs by grapefruit juice is, presumably, the inhibition of cyto-chrome P4503A4 in the small intestine and only to a minor extent affected by P-glycopro-tein function. There are dose-dependent and time-dependent effects of grapefruit juice on cytochrome P4503A4. Since biosynthesis of new cytochrome P4503A4 is necessary, the duration of the interaction is consistent with the pharmacological mechanism of interac-tion; inhibition of enzyme activities by grapefruit juice persists for approximately 3 days.