Study On The Bioequivalence In Human Of Donepezil Hydrochloride And Drug Interaction

Objective: To develop and validate a rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) method for quantification of Donepezil Hydrochloride in human plasma. Then apply this method in a pharmacokinetic and bioavailability study. Which would Provide evidences for new drug approval and clinical use. To evaluate pharmacokinetic character after Donepezil Hydrochloride and Amlodipine Bensylate administrated in combination, which would Provide reference for use drug randomly.Methods:①A LC-MS method was established for quantification of Donepezil Hydrochloride in human plasma.The plasma concentrations of donepezil hydrochloride were determined at different time points.②Twenty male healthy volunteer were divided into two group randomly , A single dose of the suspension equivalent to 5mg donepezil hydrochloride dispersed tablets or a reference preparation was given in a crossover way. LC-MS method was established for quantification of Donepezil Hydrochloride in human plasma.DAS2.0 was use to calculated the pharmacokinetic parameter.The bioavailability of two formulations was estimated by variance analysis, two-one side t-test and (1-2α) confidence intervals to main pharmacokinetic parameters.③To analysis the pharmacokinetic character of 8 volunteers who were administrated the donepezil Hydrochloride and amlodipine bensylate.Results :①The main pharmacokinetic parameters were calculated for experimental and the reference preparations were as following:t1/2 were (57.38±15.27), (59.27±27.02) h; Tmax (3.4±1.42), (3.75±2.73) h; Cmax were (9.56±2.4), (9.54±2.73) ng·mL-1 AUC0-t were (602.94±190.43), (623.25±299.76) ng·h·mL-1, AUC0-∞were 652.05±216.12 ng·h/ml , 683.93±241.74 ng·h/ml , respectively. The relative bioavailability of the test formulation was (105.2±43.2) % and 102.8±42.8 %.There was no significant difference in pharmacokinetic parameters between the two formulations with Tmax(P>0.05).②The main pharmacokinetic parameters were acquired for 8 volunteer administrated the donepezil Hydrochloride and amlodipine bensylate were as following: t1/2 was 55.88±14.64h, Cmax was 9.86± 2.40 ng/ml, Tmax was 3.62±1.18 h,C0-216 was 607.07±162.44ng·h/ml,AUC0-∞was 625.39±179.55ng·h/ml,respectively.Conclusion:①The test and reference formulations of donepezil hydrochloride were bioequivalence.②The pharmacokinetic character of single and combination was similar.