Int J Clin Pharmacol Ther 1998 Mar;36(3):126-32
Grapefruit
juice increases oral nimodipine bioavailability.
Fuhr U,
Maier-Bruggemann A, Blume H, Muck W, Unger S, Kuhlmann J, Huschka C, Zaigler M,
Rietbrock S, Staib AH.
The bioavailability of dihydropyridine calcium channel blockers following oral
administration was shown to be increased by concomitant intake of grapefruit
juice for all drugs of this class tested up to now. Here we report a randomized
crossover interaction study on the effects of grapefruit juice on the
pharmacokinetics of nimodipine and its metabolites. 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). Drug concentrations in plasma withdrawn up to 24 hours postdose
were measured by GC-ECD, and model-independent pharmacokinetic parameters were
estimated. The study was handled as an equivalence problem. Point estimators and
ANOVA based 90% confidence intervals (CI) were calculated for 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. Cmax for nimodipine reached
124% of the reference period (90% CI 0.76-2.01), AUC was increased to 151% (90%
CI 114%-200%), respectively. The null hypothesis "relevant
interaction" thus could not be rejected for the primary pharmacokinetic
parameters AUC and Cmax. The ratios of metabolite AUC to parent drug AUC were
slightly reduced with grapefruit juice intake. Additionally, there was evidence
for a more pronounced hemodynamic response in the grapefruit juice period. To
avoid the interaction, nimodipine should not be taken with grapefruit juice.