caa a22 4500 475819195 CHVBK 20180406123817.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/s002280000189 doi (NATIONALLICENCE)springer-10.1007/s002280000189 Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers [Elektronische Daten] [Ping-Chuen Ho, Karabi Ghose, Dorothy Saville, Sompon Wanwimolruk] Abstract.: Objectives: To determine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of S- and R-verapamil (given as racemates) at steady state. Methods: Nine healthy male volunteers followed a randomised cross-over study comprising two treatment periods. Pretreatments of 200ml orange juice (control) or grapefruit juice twice daily for 5days and 120mg verapamil (orally) twice daily for 3days were given. On the study day, the subjects received the morning dose of verapamil with either orange juice (control) or grapefruit juice. Plasma and urine samples were collected for measurement of S- and R-verapamil and the metabolites S- and R-norverapamil. Blood pressure (BP), heart rate (HR) and PR-interval were monitored. Results: During the grapefruit juice period, the steady-state peak and trough concentrations of S-verapamil were moderately increased (peak 41±25ng ml-1 versus 26±13ng ml-1, trough 14±7ng ml-1 versus 12±6ng ml-1, P=0.08). Grapefruit juice significantly increased the area under the plasma concentration-time curve during the 12-h dose interval (AUC0-12h) of S-verapamil by 36% (292±146ng h ml-1 versus 215±102ng h ml-1, P=0.04). Similar results were obtained for peak and trough concentrations of R-verapamil. The AUC0-12h of R-verapamil was increased by 28% (1022±412ng h ml-1 versus 800±316ng h ml-1, P=0.04). Elimination half-life and renal clearance of both S- and R-verapamil were not affected. Considerable inter-subject variability in interaction was shown. There were no significant differences in the pharmacodynamic parameters (BP, HR and PR-interval). Conclusions: The present study has demonstrated an interaction between verapamil and grapefruit juice, which is likely due to an inhibition of intestinal metabolism resulting in increased oral bioavailability. Springer-Verlag, 2000 Verapamil Calcium antagonist Grapefruit juice nationallicence Ho Ping-Chuen School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand aut Ghose Karabi Department of Pharmacology, University of Otago, P.O. Box 913, Dunedin, New Zealand aut Saville Dorothy School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand aut Wanwimolruk Sompon School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand aut European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 693-698 0031-6970 56:9-10<693 2000 56 228 https://doi.org/10.1007/s002280000189 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000189 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ho Ping-Chuen School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand aut NATIONALLICENCE 700 1- Ghose Karabi Department of Pharmacology, University of Otago, P.O. Box 913, Dunedin, New Zealand aut NATIONALLICENCE 700 1- Saville Dorothy School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand aut NATIONALLICENCE 700 1- Wanwimolruk Sompon School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 56/9-10(2000-12-01), 693-698 0031-6970 56:9-10<693 2000 56 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer