Bioequivalence of Isosorbide Mononitrate Sustained Tablets in Chinese Healthy Volunteers

OBJECTIVE:To evaluate the bioequivalence of two kinds of isosorbide mononitrate sustained tablets in Chinese healthy volunteers.METHODS:According to two formulas double period crossover protocol,a total of 18 healthy volunteers were orally administered with test prepartion(T)or reference preparation(R)(40mg),1w later,they were administered with R or T by a crossover way.For multidoese trial,the patients received T or R 40mg every morning for 6 consecutive days.Blood samples were taken at 4-6 days before oral administration in the morning,and according to the protocal,the blood samples were taken at 6d after oral administration.Serum concentrations of isosorbide mononitrate were measured with validated GC-ECD.The pharmacokinetic parameters and bioavailability of two isosorbide mononitrate sustained tablets were calculated and the bioequivalence was evaluated.RESULTS:The main pharmacokinetic parameters of tested and reference isosorbide mononitrate sustained tablet in volunteers administrated with an oral single dose of 40mg were as follows:T max(4.9±1.6)and(4.9±1.2)h,C max(719.42±183.72)and(726.52±177.55)ng·mL-1,t_ 1/2(3.9±0.6)and(3.7±0.9)h,AUC_ 0-t(5 687.38±1 271.64)and(5 586.05±1 290.01)ng·h·mL-1,AUC_ 0-∞(5 831.67± 1 308.47)and(5 719.20±1 329.54)ng·h·mL-1,and computed based on AUC_ 0-t,the relative bioavailability of tested isosorbide mononitrate sustained tablet was(103.0±17.1)%.The main pharmacokinetic parameters of tested and reference isosorbide mononitrate sustained tablet in volunteers administrated with oral multi-dose of 40 mg were as follows:T max-ss(4.9±1.4)and(4.9±1.5)h,C max-ss(745.43±143.83)and(747.55±130.72)ng·mL-1,AUC ss(7 860.24± 1 827.46)and(8 104.13±1 637.35)ng·h·mL-1,and the relative bioavailability of tested isosorbide mononitrate sustained tablet was(97.1±10.9)%.Tested with Wilcoxon(T max),ANOVA and two one-sided t test(AUC,C max),the main pharmacokinetic parameters of tested and reference isosorbide mononitrate sustained tablets showed no significant differences.The 90% confidential intervals of C max and AUC_ 0-t of tested formula were 93.26%～104.33% and 95.10%～108.83%,respectively.The 90% confidential intervals of C max-ss and AUC ss of tested formula were 93.97%～105.01% and 92.24%～101.08%,respectively.CONCLUSION:Two kinds of isosorbide mononitrate sustained tablets are bioequivalent.