Bioequivalence Study Of Generic Drug Indapamide Oral Solid Preparations

Objective: No matter in Europe,America,Japan,or some emerging market countries in Asia,generic drugs have become the mainstream of drug consumption,playing an irreplaceable role in protecting the health of the people and promoting the development of medical and health care.The price of generic drugs is relatively low,and it has the economic and social benefits of improving medical service levels,reducing medical expenses,and maintaining public health.There have been many reports on the bioequivalence study of indapamide,but in its reported study,subjects selected male subjects of single sex for clinical trials,ignoring the effect of gender on experimental results;Clinical trial conditions were also selected under fasting conditions,ignoring the effect of diet on their experimental results.And AUC,C_max,and tmax are selected as the criteria for judging the equivalent.For C_max,the 90% confidence interval is generally required to be between 70% and 143%.The above various experimental requirements and equivalence criteria are inconsistent with the current relevant guidelines.Since the reform,this study is the first to strictly follow the Guidelines and the bioequivalence study of indapamide oral solid preparations.Considering a variety of factors,the bioequivalence experiment selected subjects of different genders,both under the conditions of fasting and postprandial,and the experimental results were in line with the criteria recommended by the guiding principles.At present,there is no report on the pharmacokinetic effects of sex on indapamide at home and abroad.This study is the first to analyze the pharmacokinetic effects of gender on oral administration of indapamide tablets and sustained-release tablets in healthy subjects.Provide a basis for the clinical application of Pappa ordinary tablets and sustained release tablets.Method: 1.This study established a rapid and sensitive LC-MS/MS method for the determination of indapamide concentration in human whole blood,and applied this method to the bioequivalence study of indapamide.2.A single-center,two-dose,two-sequence,two-cycle crossover experimental design was conducted.The pharmacokinetic parameters of indapamide were analysised after subjects oral administration of the test preparation and the reference preparation.Result: 1.In human whole blood,indapamide has a good linear relationship in the range of 0.1¹00 ng/m L?r>0.99?,and the lower limit of quantification is 0.1 ng·m L-1;the lower limit of quantification and the intra-and inter-assay precision of the quality control sample meet the requirements.There was no endogenous interference in whole blood,no effect on matrix effect,and high recovery rate.Whole blood samples that were placed at room temperature for 2 h and freeze-thaw at-70 ?for three times?each cycle was frozen after more than 12 hours of freezing?is stable.The sample stored at-70 ? for 50 days is stable,and the sample autosampler was stable after being placed for 70 h.2.The pharmacokinetic parameters of indapamide were analysised after subjects oral administration of the test preparation and the reference preparation.were log-transformed and analyzed by ANOVA.There was no significant difference in C_max,AUC_0-72h,and AUC_0-? between the test preparation and the reference preparation?P>0.05?;t-test showed that the test preparations AUC0-t,AUC_0-?and C_max 90% confidence intervals were also n the range of 80.00% to 125.00%.Conclusions: The indapamide tablets fasting test C_max,AUC_0-72h,and AUC_0-? 90% confidence intervals are all in the range of 80.00% to 125.00%,it can be judged that the two preparations are bioequivalent.the 90% confidence intervals of the fast-acting test of indapamide sustained-release tablets of the C_max,AUC_0-72h,and AUC_0-? are in the range of 80.00% to 125.00%,so it can be judged that the two preparations are equivalent to fasting;The 90% confidence intervals after the meal test of indapamide sustained-release tablets of the C_max,AUC_0-72h,and AUC_0-? are in the range of 80.00% to 125.00%,so it can be judged that the two preparations are equivalent after meal.