The aim of this study was to evaluate the pharmacokinetics of donepezil HCl (5 mg) in patients with moderately to severely impaired renal function (creatinine clearance: <30 ml min−1 1.73 m−2), following the administration of single oral doses.Methods
This was an open-label, non-randomized study in patients with compromised renal function (n=11), and in age- and gender-matched healthy controls (n=11). Each subject received a single oral dose of 5 mg donepezil. Blood samples for pharmacokinetic measurements were taken at specified intervals for 17 days post-dose. Concentrations of donepezil in plasma were measured by HPLC with UV detection.Results
There were no statistical differences between the two groups for any of the pharmacokinetic parameters evaluated (ANOVA). Cmax (mean±SD) was 7.7±1.2 ng ml−1 in healthy subjects and 8.3±3.2 ng ml−1 in renally impaired patients. AUC(0-∞) in healthy subjects and in renally impaired patients was 539±115 ng h ml−1 and 640±150 ng h ml−1, respectively. The mean half-life of donepezil was 86.7±23.3 h in healthy subjects and 91.3±40.9 h in the renally impaired patients. The drug was well tolerated by all study participants. There were no clinically significant changes in vital signs, clinical chemistry or ECG parameters.Conclusions
These findings suggest that the pharmacokinetics of donepezil do not change in patients with moderately to severely impaired renal function.