CONCURRENT ADMINISTRATION OF DONEPEZIL HCL AND DIGOXIN - ASSESSMENT OF PHARMACOKINETIC CHANGES

Aim The aim of this study was to examine the pharmacokinetics of donep ezil HCl and digoxin separately, and ill combination, following admini stration of single oral doses. Changes in cardiac conduction parameter s following: drug administration were also assessed. Methods This was an open-label, randomized, three-period crossover study in healthy mal e volunteers (n=12). During each treatment period, subjects received a single dose of either donepezil HCl (5 mg), digoxin (0.25 mg), or a c ombination of both drugs. Each treatment period was followed by a 2-we ek, drug-free washout period. Results All 12 volunteers completed the study without incident. No statistically significant differences ill d onepezil pharmacokinetics (C-max, t(max), AUC((0-120)), AUC((0-infinit y)) or t(1/2)) were observed when donepezil administered alone was com pared with donepezil administered ill combination with digoxin. Simila rly, no statistically significant differences ill digoxin pharmacokine tics were observed when digoxin was administered alone or in combinati on with donepezil. No clinically relevant changes in cardiac conductio n (lead II EGG) were observed in any subject during any treatment peri od. Conclusions Co-administration of single single doses of donepezil HCl (5 mg) and digoxin (0.25 mg) produced no changes in the pharmacoki netic profile of either drug. ill addition, co-administration produced Ilo changes in cardiac conduction parameters during the 24 h of telem etry monitoring following drug administration.