EFFECT OF GRAPEFRUIT JUICE AND NARINGIN ON NISOLDIPINE PHARMACOKINETICS

The bioavailability of some dihydropyridine calcium antagonists can be markedly augmented by grapefruit juice and may involve the bioflavono id naringin. The pharmacokinetics of nisoldipine coat-core tablet were studied in a Latin square-designed trial in which 12 healthy men were administered the drug with water, grapefruit juice, or encapsulated n aringin powder at the same amount as that assayed in the juice. Compar ed with water, grapefruit juice increased the maximum concentration of nisoldipine to 406% +/- 73% (mean +/- SEM; range, 107% to 836%; p < 0 .001), increased the area under the plasma concentration-time curve to 198% +/- 46% (range, 81% to 682%; p < 0.001), and reduced time to rea ch maximum nisoldipine concentration to 58% +/- 9% (range, 13% to 100% ; p < 0.01), probably by inhibition of presystemic metabolism and poss ibly by enhancement of drug dissolution. The interaction could not be predicted from baseline pharmacokinetics with water and resulted in gr eater interindividual variability. The naringin capsule did not change nisoldipine pharmacokinetics. All treatments produced minor effects o n supine blood pressure and heart rate, probably because subjects were normotensive. Current information supports the cautioning of patients about concomitant ingestion of grapefruit juice and nisoldipine.