Effect of diprafenone on the pharmacokinetics of digoxin.
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 x 1 mg) or digoxin and diprafenone (3 x 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], AUC(zero)-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, AUC(zero)-24 and Cmax respectively]. The mean relative magnitude of the increase in AUC(zero)-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.
Koytchev
R
R
Cooperative Clinical Drug Research and Development (CRO), Berlin, Germany.
Alken
R G
RG
Mayer
O
O
D018663:Adrenergic Agents / Q000378:metabolism; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004347:Drug Interactions; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011405:Propafenone / Q000031:analogs & derivatives* / Q000494:pharmacology
D018663:Adrenergic Agents; D000889:Anti-Arrhythmia Agents; C047546:diprafenone; D011405:Propafenone; D004077:Digoxin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin