Donepezil HCl, is a cholinesterase (ChE) inhibitor that is selective for acetylcholinesterase. It has recently been approved in the US and the UK for treatment of the symptoms of mild to moderate Alzheimer's disease. Digoxin is a cardiac glycoside that is commonly used in the elderly for the treatment of congestive heart failure and atrial fibrillation. Since both inhibition of ChE and digoxin can produce changes in heart rate or cardiac conduction, this study was designed to investigate any pharmacokinetic (PK) and/or pharmacodynamic (PD) interactions that might occur when donepezil and digoxin are administered concurrently.This was a randomized, single-dose, open-label, three-period crossover study. The three treatments administered were: 1) donepezil HCl (5 mg tablet); 2) digoxin (0.25 mg tablet), or 3) the concurrent administration of both drugs. Twelve healthy male volunteers were enrolled into this study. Subjects ranged in age from 19 to 44 years (mean ± SD: 28 ± 7.6 years). Characterization of donepezil and/or digoxin PK for each treatment phase (AUC 0 - 1 2 0 , C m a x , t m a x and t 1 2 ) was done by measuring concentrations of each drug in plasma samples collected over a 120-h period following drug administration. Donepezil was quantified by HPLC. Digoxin was measured by RIA. PD was assessed by telemetry (Lead II, ECG), beginning 1 h prior to drug administration, and continuing for 24-h after administration. Lead II rhythm strips were recorded at specified times to measure heart rate and duration of PR, QRS and QTc intervals.Donepezil PK were essentially identical when donepezil was administered alone or concurrently with digoxin. Digoxin PK were likewise unchanged by co-administration of donepezil. No differences in heart rate, PR, QRS, or QTc intervals were observed in any of the subjects, for any of the treatments during the 24 hours of monitoring following drug administration.The concurrent administration of donepezil and digoxin produced no PK or PD interactions.