RELATIONSHIP BETWEEN TIME OF INTAKE OF GRAPEFRUIT-JUICE AND ITS EFFECT ON PHARMACOKINETICS AND PHARMACODYNAMICS OF FELODIPINE IN HEALTHY-SUBJECTS

In this randomised, cross-over study, in nine healthy males given felo dipine ER 10 mg PO 200 mi grapefruit juice was found to increase the p lasma levels of felodipine even when the juice was taken 24 hours befo re the drug. Grapefruit juice drunk simultaneously with and 1, 4, 10 o r 24 hours before the drug administration resulted in a 32-99% increas e in mean C-max values of felodipine, relative to concomitant water an d felodipine intake. The effect on AUC was also significant when juice was taken up to 10 h before the drug. The effect of the interaction d ecreased with increasing time between juice and drug intake. All treat ments produced a significant decrease in diastolic blood pressure and an increase in heart rate in comparison with morning basal values. The change in haemodynamic variables was approximately the same after all treatment combinations. Headache was reported more frequently after t reatments including grapefruit juice.