caa a22 4500 477057160 CHVBK 20180405111349.0 cr unu---uuuuu 170330e19960501xx s 000 0 eng 10.1007/s002280050093 doi (NATIONALLICENCE)springer-10.1007/s002280050093 Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine [Elektronische Daten] [J. K. Madsen, J. D. Jensen, L. W. Jensen, E. B. Pedersen] Objective: In a double blind, randomised, placebo-controlled, cross-over study 12 healthy male volunteers were allocated to receive felodipine + placebo, cyclosporine + placebo, and felodipine + cyclosporine in order to investigate the interaction between the calcium channel blocker felodipine and cyclosporine as it affects the pharmacokinetics of felodipine, dehydrofelodipine, and cyclosporine, and 24-hour blood pressure measurements. Methods: Single doses of cyclosporine (capsules, 5 mg/kg body weight) and of felodipine (extended release (ER) tablets 10 mg) were given at a 1-2 week interval. Plasma drug concentrations were followed for 2 days after drug intake. Results: For cyclosporine, Cmax was increased after combined treatment (16%) compared to cyclosporine alone, but felodipine did not influence other kinetic parameters of cyclosporine. For felodipine, combined treatment with cyclosporine and felodipine increased AUC and Cmax (58% and 151%, respectively) and lowered mean residence time (24%) significantly compared to felodipine alone. For the metabolite dehydrofelodipine, too, AUC and Cmax were increased after the combined treatment (43% and 94%, respectively). Mean 24-hour systolic and diastolic blood pressures were significantly lower after felodipine, both when felodipine was given alone (121/68 mmHg) and in combination with cyclosporine (122/68 mmHg) compared to cyclosporine alone (127/73 mmHg). Conclusion: A combined single dose of cyclosporine and felodipine in healthy subjects increased the AUC and Cmax of felodipine suggesting a cyclosporine-induced decrease in the first-pass metabolism of felodipine, whereas the AUC of cyclosporine was only slightly increased by felodipine. Springer-Verlag Berlin Heidelberg, 1996 Key words Cyclosporine nationallicence Felodipine nationallicence dehydrofelodi-pine nationallicence pharmacokinetics nationallicence blood pressure nationallicence drug interaction nationallicence Madsen J. K. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut Jensen J. D. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut Jensen L. W. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut Pedersen E. B. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut https://doi.org/10.1007/s002280050093 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050093 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Madsen J. K. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut NATIONALLICENCE 700 1- Jensen J. D. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut NATIONALLICENCE 700 1- Jensen L. W. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut NATIONALLICENCE 700 1- Pedersen E. B. Research Laboratory for Nephrology and Hypertension, Aarhus University Hospital, Aarhus, Denmark, DK aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer