Pharmacokinetic and pharmacodynamic profile of donepezil HCl following evening administration.

摘要: Aims The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics single daily doses donepezil (5 10 mg) each evening for 28 consecutive days. A secondary measure plasma protein binding at steady state. Methods This a double-blind, randomized, multiple-dose in healthy male (n=13) female (n=3) volunteers. Subjects were randomized receive, once daily, either oral 5 mg 28 days or 7 days followed by 10 mg 21 days. All administered evening. Donepezil concentrations determined HPLC with UV detection equilibrium dialysis, respectively. Inhibition acetylcholinesterase (AChE) activity red blood cell (rbc) membranes assessed using specific radioenzyme assay. Results The linear, dose proportional stationary over course study. Mean Cmax, tmax , AUC(0–24), t½ Vλz /F state 34.1 ng ml−1, 3.0 h, 634.8 ng h ml−1, 72.7 h, 11.8 l kg−1, respectively, group 60.5 ng ml−1, 3.9 h, 1127.8 ng h ml−1, 73.5 h 11.6 l kg−1, group. Accumulation drug observed 14–21 days, until achieved. direct consistent relationship between concentration percentage rbc-AChE inhibition during 24 h evaluation period, indicating no hysteresis pharmacodynamics. The pharmacodynamic parameters, Emin, Emax Ess, 62.2%, 71.8% 65.3%, dose, 74.7%, 83.6% 77.8%, dose. 95.6% bound state. high capacity low affinity, neither nor time dependent. Both dosage regimens well tolerated; clinically significant changes laboratory vital sign parameters any subject. Conclusions The measured pharmacokinetic both 5 day−1 are good agreement previous results obtained morning administration, dosing effect.