An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function.

AIM The aim of this study was to evaluate the pharmacokinetic profile of donepezil HCl (5 mg) in patients with impaired hepatic function, following the administration of single oral doses. METHODS This was an open-label, non-randomized study comparing the pharmacokinetic profile of donepezil in male volunteers with chronic compensated cirrhosis of the liver (n = 10) to that in healthy age- and sex-matched controls (n = 10). Each subject received a single 5 mg oral dose of donepezil. Blood samples for pharmacokinetic analyses were taken at specified intervals up to 120-h post-dose. Concentrations of donepezil in plasma were determined by HPLC with UV detection. RESULTS No statistically significant differences in donepezil pharmacokinetics were observed between hepatically impaired patients and normal subjects, with the exception of Cmax. The hepatically impaired patients showed a statistically significant, but not clinically significant, higher mean Cmax value of 6.6 ng ml(-1) compared with the control group, which had a mean Cmax value of 4.8 ng ml(-1) (P=(0.022). This represented an increase of 37.5%. The observed changes in AUC values were smaller and not statistically different. The AUC(0-120) and AUC(0-infinity) were 7% and 21% larger in the hepatically impaired patients than in the normal subjects, respectively, although clearance and volume of distribution were almost identical in the two groups. The t1/2 increased by 20%, but this change was also not statistically significant. Donepezil was equally well tolerated by all subjects. CONCLUSIONS This study demonstrates that compromised hepatic function does not produce clinically significant changes in the pharmacokinetics of donepezil following single-dose administration. These results suggest that the administration of donepezil to patients with hepatic disease in clinical practice should not require any dosing modifications.