When atrial fibrillation persists on digoxin therapy, inadequate digoxin dose is suspected. Plasma levels of digoxin for confirmation are taken after 6 hours of last dose taking into consideration which of the following?

Ans: B (Rate of distribution) Ref: Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice by Sumner, 4th edition, 2010, pg: 106 and KD TripathiExplanation:Pharmacokinetics of DigoxinImmediately after administration, digoxin must distribute into the blood and then to tissues in the body.This results in initial concentrations that are much higher than and which do not show a log linear correlation with post- distributional concentrations.There are large differences between trough and distribution concentrations even for very long half-life drugs.Digoxin can have post dose peak concentrations of 3 - 5 ng per ml in patients with trough concentration of less than 1 ng per ml.There are also greatly different concentrations effect relationships between distribution and post-distributional concentrations at the site of action.Concentrations drawn during the distribution phase (first 4 to 6 hours) will not correlate with the effects because they do not reflect the effective concentration.The volume of distribution of cardiac glycosides is large, e.g. 6-8 Ukg in case of digoxin.All are concentrated in the heart {-20 times than plasma), skeletal muscle, liver and kidneyDigoxin is primarily excreted unchanged by the kidney: mainly by glomerular filtration; rate of excretion is altered parallel to creatinine clearance.Cardiac glycosides are cumulative drugs.When maintenance doses are given from the beginning, steady state levels and full therapeutic effect are attained after 4 x t 1/2 , i.e. 6-7 days for digoxin.