Steady-state pharmacokinetics, pharmacodynamics and tolerability of donepezil hydrochloride in hepatically impaired patientsCorrespondence Josephine F. Reyes, DVM, Associate Director, Clinical Pharmacology, Eisai Medical Research Inc., 55 Challenger Road, Ridgefield Park, NJ 07660, USA Tel: +1 201 287 2157 Fax: +1 201 692 9183 E-mail: In this single-centre, multiple-dose, open-label study, patients with impaired hepatic function (Child Pugh grade A or B) and healthy controls (matched by gender, age and weight to the hepatically impaired patients) received a single 5 mg dose of donepezil on day 1 and then donepezil HCl 5 mg once daily from days 6 to 29. PK and PD (determination of erythrocyte acetylcholinesterase inhibition) parameters were evaluated on days 1 and 29. Treatment-emergent adverse events (AEs), vital signs, physical examination and clinical laboratory test parameters were monitored throughout the study.The PK of a single 5 mg dose of donepezil HCl have previously been investigated in male patients with hepatic impairment due to alcoholic cirrhosis [15]. The present study featured a number of modifications from this earlier study that were intended to increase the relevance of its findings to the clinical setting. The present study enrolled both male and female patients with stable hepatic impairment due to any causes, more closely representing the hepatically impaired population encountered in the clinic. In addition, 24 daily doses of 5 mg donepezil HCl were chosen for this study rather than the single dose used in the earlier study. This dose was selected because of its demonstrated efficacy in clinical trials [3 5], leading to its approved use for the treatment of mild to moderate AD [12], and the likelihood that it would be well tolerated by hepatically impaired patients [15]. The use of this dose also avoided exposing subjects to unnecessary levels of AChE inhibition.
