The authors provided evidence that the pharmacokinetics of digoxin are influenced by daily rhythms. Using doses of 0.125 mg digoxin by the oral route, after 12 hours they found a statistically higher serum digoxin concentration in the minimum before administration of the morning dose and in the maximum concentration after this dose, as compared with the minimal and maximal concentration before and after administration of the same dose in the evening. The other pharmacokinetic parameters--the area beneath the curve of serum concentrations, the time before the maximum concentration was attained and the total plasma clearance of digoxin did not differ. This chrono-pharmacokinetic relationship in compensated cardiac patients was comparable with data in the literature pertaining to healthy volunteers. To conclude it may be said that on administration of major does in the morning there is a greater risk of serum concentrations beyond the therapeutic range than during the administration of the same amount of digoxin in the evening.

Keywords: Aged; Circadian Rhythm; Digoxin /administration & dosage/; Drug Administration Schedule; Female; Heart Diseases /drug therapy/; Humans; Male; Middle Aged