caa a22 4500 477057446 CHVBK 20180405111350.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/s002280050075 doi (NATIONALLICENCE)springer-10.1007/s002280050075 Effect of diprafenone on the pharmacokinetics of digoxin [Elektronische Daten] [R. Koytchev, R.-G. Alken, O. Mayer] This study was conducted to investigate the effect of diprafenone on the steady-state pharmacokinetics of digoxin. Twelve healthy men, all rapid hydroxylators of debrisoquine, received digoxin (0.5 mg per day over 7 days with a loading dose of 2 × 1 mg) or digoxin and diprafenone (3 × 100 mg per day) in three different phases, without a wash-out period (phase 1, digoxin alone; phase 2, digoxin + diprafenone; phase 3, digoxin alone). Blood and urine samples were collected for pharmacokinetic analyses. Diprafenone caused a statistically significant increase in digoxin trough concentrations [1.4 (SD 0.2) vs 1.6 (0.3) ng ⋅ml−1], AUC0-24 values [41 (7) vs 48 (9) ng⋅h⋅ml−1 and Css-max [3.9 (0.6) vs 5.5 (0.9) ng⋅ml−1]. In all volunteers the parameters tended to return to the original values after administration of diprafenone was discontinued [1.4 (0.3) ng⋅ml−1, 39 (11) ng⋅h⋅ml−1, and 3.9 (1.1) ng⋅ml−1 for trough concentration, AUC0-24 and Cmax respectively]. The mean relative magnitude of the increase in AUC0-24 and trough concentration values corresponded to the mean relative decrease in the renal clearance of digoxin (in both cases approximately 20%). This suggests that the increase in AUC and Css was caused by reduced renal clearance of digoxin. Springer-Verlag Berlin Heidelberg, 1996 Key words Diprafenone nationallicence Digoxin nationallicence Drug interaction nationallicence antiarrhythmics nationallicence human pharmacokinetics nationallicence Koytchev R. Cooperative Clinical Drug Research and Development (CRO), Waldstrasse 23-24, D-13403 Berlin, Germany, DE aut Alken R.-G Cooperative Clinical Drug Research and Development (CRO), Waldstrasse 23-24, D-13403 Berlin, Germany, DE aut Mayer O. Department of Clinical Pharmacology, University Hospital, Pilsen, Czech Republic, XX aut https://doi.org/10.1007/s002280050075 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050075 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Koytchev R. Cooperative Clinical Drug Research and Development (CRO), Waldstrasse 23-24, D-13403 Berlin, Germany, DE aut NATIONALLICENCE 700 1- Alken R.-G Cooperative Clinical Drug Research and Development (CRO), Waldstrasse 23-24, D-13403 Berlin, Germany, DE aut NATIONALLICENCE 700 1- Mayer O. Department of Clinical Pharmacology, University Hospital, Pilsen, Czech Republic, XX aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer