THE INTERACTION EFFECT OF GRAPEFRUIT JUICE IS MAXIMAL AFTER THE FIRSTGLASS

Objective: To compare the acute effect of grapefruit juice intake on t he pharmacokinetics and haemodynamic effects of felodipine ER tablets with the interaction after 14 days intake of drug with juice. Methods: Twelve healthy male volunteers were included in this cross-over trial and randomly allocated to a daily intake of a 10-mg felodipine extend ed release tablet with water or grapefruit juice for 14 days. The two study periods were separated by at least 14 days. The pharmacokinetics of felodipine and dehydrofelodipine, as well as the haemodynamic effe cts of the drug, were studied during day 1 and 14 in each period. Resu lts: Similarly to previous single-dose studies, the treatment during t he first day with grapefruit juice increased the AUC (+73%) and C-max (+138%) of felodipine when compared with the control treatment. On day 14 a similar effect of grapefruit juice was observed, with an increas ed AUC(24),(+57%) and C-max (+114%) of felodipine compared with the co ntrol experiment. A significant accumulation of felodipine occurred du ring both the control (+37%) and grapefruit juice (+25%) period. The e xtent of accumulation was not significantly different in the two treat ment periods. The pharmacokinetics of the metabolite dehydrofelodipine were affected to a similar extent by the juice on day 1 and day 14.Th e first dose of felodipine together with grapefruit juice was associat ed with a significant additional increase in heart rate when compared with the control therapy, whereas there was no additional effect on bl ood pressure when therapy included grapefruit juice. On day 14 the int ake of drug with juice resulted in an additional increase in heart rat e and reduction in diastolic blood pressure in comparison with the con trol experiment. Furthermore, the vascularly related adverse events we re more frequent in the period including grapefruit juice. Conclusion: The interaction between grapefruit juice and felodipine appears to be already fully developed after the first glass of grapefruit juice, as the change in pharmacokinetics in comparison with the control experim ent is similar on day I and on day 14. Concomitant intake of 10 mg fel odipine ER and the juice is associated with increased haemodynamic eff ects in healthy subjects both after a single dose and following 14 day s of concomitant intake.