Influence of Grapefruit Juice on the Plasma Concentration of Nifedipine

Recent studies have suggested that grapefruit juice increases the plasma concentration of a number of drugs, such as dihydropyridine calcium antagonists. However, very little is known about the interaction between grapefruit juice and nifedipine in Japanese. Here, the influence of grapefruit juice on the pharmacokinetics of two slow-release formulations of nifedipine [tablets (NFL) and fine granules (NFR)] were investigated in 15 healthy Japanese male volunteers. The following results were obtained: (1) The plasma level of nifedipine after oral administration of NFL or NFR with water showed a sustained plateau. Intake of 100% grapefruit juice with NFL did not affect the AUC of nifedipine. In contrast, the AUC was significantly altered by concomitant intake of 100% grapefruit juice with NFR.(2) When 30% grapefruit juice in distilled water was orally administered with NFR, there was no change in the pharmacokinetics of nifedipine compared to administration with water alone.(3) The effect of 100% grapefruit juice taken one hour before, one hour after, and at the time of NFR dosing was investigated. There were no significant differences in the pharmacokinetics of nifedipine when 100% grapefruit juice was taken one hour before or at the time of dosing. On the other hand, tmax was significantly increased when 100% grapefruit juice was taken one hour after dosing compared to that at the time of dosing. In conclusion, 100% grapefruit juice increases the plasma concentration of oral NFR in Japanese.