Effect of grapefruit pulp on the pharmacokinetics of the dihydropyridine calcium antagonists nifedipine and nisoldipine

Abstract

The effect of the intake of 200 g of grapefruit pulp (corresponding to one grapefruit) on the pharmacokinetics of the calcium antagonists nifedipine (NF) and nisoldipine (NS) were investigated in 8 healthy Japanese male volunteers. A crossover design was used for the study: group I did not ingest any grapefruit (control group); group II ingested grapefruit 1 h after drug administration; and group III ingested grapefruit 1 h before drug administration. The intake of grapefruit pulp increased the plasma concentrations of both NF and NS, an effect that has previously been reported with grapefruit juice. The increase was most marked when grapefruit was eaten before drug administration. For both NF and NS, subjects who ingested grapefruit 1 h before drug administration exhibited a greater C max and AUC 0-24 than did subjects in the control group. For NF, the C max was 1.4 times higher and the AUC 0-24 1.3 times larger in group III than in group I. For NS, the C max was 1.5 times higher and the AUC 0-24 1.3 times larger in group III than in group I. The increase in the AUC 0-24 was significant for both drugs (p<0.05). The finding that the ratios of C max and AUC 0-24 for unchanged drug and metabolites did not vary greatly among the three groups for either drug suggests that the increase in serum concentration produced by grapefruit intake may be due to other factors than an inhibitory effect on drug metabolism. Also, the increases in C max and AUC 0-24 of NS produced by grapefruit intake were smaller than those produced by grapefruit juice intake, indicating that grapefruit pulp and juice have different effects on the pharmacokinetics. © 2002 The Pharmaceutical Society of Japan.