caa a22 4500 477056830 CHVBK 20180405111348.0 cr unu---uuuuu 170330e19961001xx s 000 0 eng 10.1007/s002280050183 doi (NATIONALLICENCE)springer-10.1007/s002280050183 Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers [Elektronische Daten] [M. Josefsson, A.-L. Zackrisson, J. Ahlner] Abstract.: Objective: This study was performed to assess whether coadminstration with grapefruit juice significantly affects the pharmacokinetics of amlodipine, a dihydropyridine class calcium antagonist with slow absorption, distribution and low plasma clearance. The primary objective was to evaluate whether short exposure to grapefruit juice could affect the metabolism of amlodipine to an extent similar to that previously demonstrated for other dihydropyridines (e.g. felodipine, nisoldipine, nitrendipine). Methods: Twelve healthy male volunteers followed a randomised, open crossover study design, comparing the effect of a single oral dose of amlodipine (5 mg) taken together with a glass of grapefruit juice (250 ml) vs water. Blood samples to determine plasma concentration were taken and blood pressure (BP) and heart rate (HR) were measured throughout the study. Results: When amlodipine was coadministered with grapefruit juice, Cmax was 115% and AUC(0-72 h) was 116% compared with water, but tmax was not significantly changed. There were no significant differences in BP and HR between the two treatments. A small decrease in diastolic BP, however, was observed in both treatments 4-8 h after drug administration, coinciding with Cmax, but this was normalised after 12 h. The BP reduction seen was compensated by a slight increase in HR, which remained throughout the study. Conclusion: An interaction between grapefruit juice and amlodipine was demonstrated. The haemodynamic data showed that a dose of 5 mg was sufficient to achieve a BP reduction in healthy subjects, but the increase in amlodipine plasma concentration seen after intake of grapefruit juice was too small to significantly affect BP or HR. The clinical significance of this food/drug interaction, however, cannot be ignored since there is considerable variation between individuals and a more extensive intake of grapefruit juice might give more pronounced effects. Springer-Verlag Berlin Heidelberg, 1996 Key words Dihydropyridine nationallicence Amlodipine nationallicence Grapefruit juice nationallicence flavonoids nationallicence interaction nationallicence pharmacokinetics nationallicence Josefsson M. Department of Clinical Pharmacology, Faculty of Health Sciences, S-581 85 Linköping, Sweden, SE aut Zackrisson A.-L Department of Clinical Pharmacology, Faculty of Health Sciences, S-581 85 Linköping, Sweden, SE aut Ahlner J. Department of Clinical Pharmacology, Faculty of Health Sciences, S-581 85 Linköping, Sweden, SE aut https://doi.org/10.1007/s002280050183 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050183 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Josefsson M. Department of Clinical Pharmacology, Faculty of Health Sciences, S-581 85 Linköping, Sweden, SE aut NATIONALLICENCE 700 1- Zackrisson A.-L Department of Clinical Pharmacology, Faculty of Health Sciences, S-581 85 Linköping, Sweden, SE aut NATIONALLICENCE 700 1- Ahlner J. Department of Clinical Pharmacology, Faculty of Health Sciences, S-581 85 Linköping, Sweden, SE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer