Oral Digoxin Onset of Action
Oral digoxin has an onset of action of 0.5 to 2 hours, with peak therapeutic effect occurring at 2 to 6 hours after administration. 1
Pharmacokinetic Timeline
Absorption phase: Peak serum concentrations occur at 1 to 3 hours following oral administration, with 60-80% bioavailability from tablets 1
Distribution phase: A 6 to 8-hour tissue distribution phase follows drug administration, during which early high serum concentrations do not reflect the concentration at the site of action 1
Therapeutic effect timing: The documented onset for ventricular response rate control in atrial fibrillation, inotropic effects, and electrocardiographic changes begins at 0.5 to 2 hours, reaching peak effect at 2 to 6 hours 1
Clinical Implications for Rate Control
Delayed meaningful effect: When using oral digoxin for rate control in atrial fibrillation, there is a delay of at least 60 minutes before onset of therapeutic effect in most patients, with peak effect not developing for up to 6 hours 2
Not first-line for acute management: Digoxin is no longer considered first-line therapy for rapid management of atrial fibrillation due to this delayed onset and reduced efficacy in high sympathetic tone states 2
Preferred alternatives for acute control: Beta-blockers (metoprolol, propranolol, esmolol) or nondihydropyridine calcium channel blockers (diltiazem, verapamil) are preferred for acute rate control as they act more rapidly, with onset times of 2-7 minutes for IV administration 3, 2
Steady-State Considerations
Chronic dosing timeline: For oral maintenance therapy without a loading dose, steady-state serum concentrations develop over approximately 2 days (as indicated by the maintenance dose onset of "2 days" in chronic therapy) 3
Elimination half-life: The half-life of digoxin in patients with normal renal function is 1.5 to 2.0 days (36-48 hours), which determines the time to steady state 1, 4
Important Caveats
Food effects: When taken with meals, the rate of absorption is slowed but total amount absorbed is usually unchanged; however, meals high in bran fiber may reduce the amount absorbed 1
Post-distribution equilibrium: With chronic use, steady-state post-distribution serum concentrations equilibrate with tissue concentrations and correlate with pharmacologic effects, making them useful for therapeutic monitoring 1
Renal function impact: In patients with impaired renal function, the half-life is prolonged to 3.5 to 5 days, significantly affecting both onset and duration of action 1