GRAPEFRUIT JUICE INCREASES ORAL NIMODIPINE BIOAVAILABILITY

The bioavailability of dihydropyridine calcium channel blockers follow ing oral administration was shown to be increased by concomitant intak e of grapefruit juice for all drugs of this class tested up to now. He re we report a randomized crossover interaction study on the effects o f grapefruit juice on the pharmacokinetics of nimodipine and its metab olites. Eight healthy young men (4 smokers/4 nonsmokers) were included . Nimodipine was given as a single 30 mg tablet (Nimotop) with either 250 ml of water or 250 ml of grapefruit juice (751 mg naringin/l). Dru g concentrations ig plasma withdrawn up to 24 hours postdose were meas ured by GC-ECD, and model-independent pharmacokinetic parameters were estimated. The study was handled as an equivalence problem. Point esti mators and ANOVA based 90% confidence intervals (CI) were calculated f or the test (= grapefruit juice period) to reference (= water period) ratios using dose-normalized concentrations. The absence of a relevant interaction was assumed if the CIs were within the 0.67 - 1.50 range. C-max for nimodipine reached 124% of the reference period (90% CI 0.7 6 - 2.01), AUC was increased to 151% (90% CI 114% - 200%), respectivel y. The null hypothesis ''relevant interaction'' thus could not be reje cted for the primary pharmacokinetic parameters AUC and C-max. The rat ios of metabolite AUC to parent drug AUC were slightly reduced with gr apefruit juice intake, Additionally, there was evidence for a more pro nounced hemodynamic response in the grapefruit juice period. To avoid the interaction, nimodipine should not be taken with grapefruit juice.