Morning-evening administration time differences in digoxin kinetics in healthy young subjects.
Digoxin, frequently used in the treatment of congestive heart failure, has a very narrow therapeutic index. We studied the differences in digoxin pharmacokinetics when ingested in the morning versus evening. A single digoxin (0.25 mg) dose was given orally to the same group of 10 diurnally active healthy (6 male and 4 female) volunteers in the morning at 08:00 and evening at 20:00 in separate experiments scheduled 2 weeks apart. Blood samples were collected at specific times for 48h after each timed dose; digoxin was determined by radioimmunoassay (RIA). Maximum plasma concentration Cmax; Tmax, the time to reach Cmax; area under plasma concentration curve AUC; and elimination half-time T1/2 of digoxin were determined. Tmax was statistically significantly shorter (54 min) following 08:00 dosing com pared to 20:00 dosing (96 min). Although the Cmax was higher after morning than evening dosing, it was not significantly so. No other parameter of digoxin pharmacokinetics except Tmax exhibited administration time dependency.
Erol
K
K
Osmangazi University, School of Medicine, Department of Pharmacology, Eskisehir, Turkey.
Kiliç
F S
FS
Batu
O S
OS
Yildirim
E
E
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019454:Chronotherapy; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012449:Safety
D002316:Cardiotonic Agents; D004077:Digoxin