Takahiko Tanigawa

Effects of grapefruit juice on the pharmacokinetics of the calcium channel blockers nifedipine and nisoldipine

This study was designed to investigate the effects of marketed grapefruit juice (GFJ) on the pharmacokinetics of nifedipine and nisoldipine and of the time between ingestion of GFJ and drug administration in Japanese subjects. Two groups of eight healthy men received single oral doses of nifedipine 20 mg or nisoldipine 10 mg on four dosing schedules: (1) with GFJ; (2) 1 hour after drinking GFJ; (3) 1 hour before drinking GFJ; and (4) with water alone. GFJ had relatively minor effects on nifedipine pharmacokinetics, whereas plasma nisoldipine concentrations were increased by drug administration with or within 1 hour before or after GFJ ingestion. Nifedipine and nisoldipine were well tolerated in each dosing schedule, suggesting that no clinically relevant interactions occurred. However, it would be wise to avoid drinking GFJ within 1 hour before or after taking nisoldipine, because the combination increases plasma drug concentrations. Inhibition of the metabolism of dihydropyridines could not be ruled out, because bioflavonoids and furanocoumarines were present in the marketed GFJ. The observed differences in the effects of GFJ on the pharmacokinetics of nifedipine and nisoldipine in this parallel study appear to be attributable to the differences in their bioavailability.