两种单硝酸异山梨酯缓释片在人体中的生物等效性试验研究

Bioequivalence of two isosorbide mononitrate sustained-release tablets in human body

目的:本试验旨在研究两种单硝酸异山梨酯缓释片在人体中的生物等效性。方法:采用双周期随机自身交叉试验设计。分别给予受试者受试制剂或参比制剂(均含单硝酸异山梨酯60 mg),采用气相色谱法测定给药后不同时间的单硝酸异山梨酯的血药浓度。计算药动学参数。结果:(1)单硝酸异山梨酯参比制剂(R)与受试制剂(A)的主要药代动力学参数C max(772.95±106.68 vs.767.84±108.54)ng/mL、T max(5.78±0.81 vs.5.72±0.83)h、AUC 0-36(11219.57±1731.61 vs.10897.97±1670.59)ng·h^-1·mL^-1和AUC 0→∞(12432.67±2050.36 vs.11865.56±1937.85)ng·h^-1·mL^-1均较为接近;(2)T max经非参数检验,两种制剂间差异无统计学意义(P>0.05);(3)AUC 0-36、AUC 0→∞和C max在不同制剂间和不同周期间差异无无统计学意义(P<0.05);(4)受试制剂AUC 0-36和AUC 0→∞的90%可信区间均未超出参比制剂相应AUC 0-36和AUC 0→∞的80%~125%的范围;(5)受试制剂的C max的90%可信区间,也未超出参比制剂C max的70%~143%的范围。受试制剂对参比制剂的平均相对生物利用度F(以AUC 0-36作为评价依据)为102.9%。结论:受试制剂单硝酸异山梨酯缓释片与等剂量的参比制剂在人体的吸收速度和吸收量差异无统计学意义,两药具有生物等效性。

Objective:To study the bioequivalence of two isosorbide mononitrate sustained-release tablets in human body.Methods:The double period randomized self crossover design was used.Subjects were given 60 mg isosorbide mononitrate of test preparation or reference preparation respectively,and the blood concentration of isosorbide mononitrate at different time after administration was determined by gas chromatography.The pharmacokinetic parameters were calculated.Results:The main pharmacokinetic parameters C max(772.95±106.68 vs.767.84±108.54)ng/mL,T max(5.78±0.81 vs.5.72±0.83)h,AUC 0-36(11,219.57±1,731.61 vs.10,897.97±1,670.59)ng·h/mL and AUC 0→∞(12,432.67±2,050.36 vs.11,865.56±1,937.85)ng·h/mL of the isosorbide monosorbate reference preparation(R)and the test preparation(A)were closed.There was no significant difference in T max between the two preparations by nonparametric test(P>0.05).AUC 0-36,AUC 0→∞and C max were no significant difference between different formulations and different periods(P<0.05).The 90%confidence intervals of the test preparations AUC 0-36 and AUC 0→∞did not exceed the range of 80%to 125%of the corresponding AUC 0-36 and AUC 0→∞of the reference preparation.The 90%confidence interval for the C max of the test formulation did not exceed the range of 70%and 143%of the C max of the reference formulation.The average relative bioavailability F of the test preparation to the reference preparation(based on AUC 0-36)was 102.9%.Conclusion:There are no significant difference in the absorption rate and absorption between the test preparation isosorbide mononitrate sustained-release tablets and the equivalent dose of the reference preparation(isosorbide mononitrate sustained release tablets).The two drugs are bioequivalent.