Study On Bioequivalence Of Capsule Coated Adefovir Dipivoxil Tablet

Objective:This study was designed to compare the bioavailability of capsuledadefovir dipivoxil tablets produced by GlaxoSmithKline Co., Ltd.(Tianjin) relativesto the non-capsuled original formulation, to determine whether there isbioequivalence between two formulation.Methods: An open, randomized, double-cross, two-cycle, single dose, one-center trial,7days of wash-out period between two study periods was used. There is a total of20subjects， and20mg of test formulation or reference formulation was orallyadministrated in the same subject in different periods. Plasma concentration afteradministration of adefovir dipivoxil at different time points was measured by usingHPLC-MS/MS method. Pharmacokinetic parameters was calculated and analysed byusing DAS2.1. Bioequivalence analysis was determined according to the AUC0-∞,AUC0-t, Cmaxand Tmaxafter administration.Results: In20healthy subjects who orally administrated the reference formulation (R)of non-capsuled adefovir dipivoxil tablets and test formulation (A) of capsuledadefovir dipivoxil tablets, the main pharmacokinetic kinetic parameters of Cmax, Tmax,T1/2, AUC048, AUC0was45.36.81and43.37.47μg·L-1;1.030.33and1.850.75h；8.613.15and9.142.74h;520.7123.8and514.0130.5μg·h·L-1；549.5134.1and548.6143.0μg·h·L-1, respectively. Results of Cmax, AUC048andAUC0→two-sided t test showed that the thand tlwere greater than one-tail t0.05,90%confidence interval of test formulation’s AUC048and AUC0→were within thereference preparation’s AUC048and AUC0→80%~125%range; so was the Cmaxin70%~143%range. Tmaxwas analysed by non-parametric test (paired Wilcoxonmethod), and found that there were differences between different formulations(P<0.05), Tmaxwas prolonged after adefovir dipivoxil tablets were capsuled, whichmay be dued to the effect of capsule shell on the drug absorption rate. These resultssuggest that there were no significant differences between test formulation andreference formulation of in absorbance of human body. The bioavailability of test formulation relatives to reference formulation, F (evaluated as AUC048) was98.8%.Conclusion: There was bioequivalence between capsuled adefovir dipivoxil tabletsproduced by GlaxoSmithKline Co., Ltd.(Tianjin) and the non-capsuled originalformulation.