Effect of diprafenone on the pharmacokinetics of digoxin
| Autor: | R. Koytchev, O. Mayer, R.-G. Alken |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Digoxin Debrisoquin Cmax Urine Pharmacology Loading dose Mixed Function Oxygenases chemistry.chemical_compound Adrenergic Agents Pharmacokinetics Cytochrome P-450 Enzyme System Propafenone medicine Humans Pharmacology (medical) Trough Concentration Drug Interactions Diprafenone digestive oral and skin physiology General Medicine Phenotype chemistry Cytochrome P-450 CYP2D6 Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 50(1-2) |
| ISSN: | 0031-6970 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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