盐酸氨基葡萄糖两制剂人体生物等效性研究

Bioequivalence of Glucosamine Hydrochloride Preparations in Healthy Volunteers

目的:比较两种氨基葡萄糖制剂的人体生物等效性。方法:20名健康男性志愿者随机交叉单剂量口服氨基葡萄糖颗粒(受试制剂)与氨基葡萄糖胶囊(参比制剂)0.75 g,采用邻苯二甲醛/3-巯基丙酸衍生化后的LC-MS/MS法测定人血浆中氨基葡萄糖浓度,用DAS 2.1.1软件计算药动学参数和生物利用度。结果:口服氨基葡萄糖受试制剂与参比制剂后的人体药动学参数分别为:C_(max)(1 015±306)和(1 026±470)ng·ml～,t_(max)(2.40±1.20)和(2.80±1.37)h,t_(1/2β)(1.24±0.53)和(1.20±0.32)h,AUC_(0～t)(4 504±1 303)和(4 315±1 410)ng·h·ml～,AUC_(0～∞)(4 579±1 275)和(4 341±1 407)ng·h·ml^(-1)。受试制剂的相对生物利用度为(114.1±44.8)%。受试制剂AUC_(0～1)的90%置信区间在参比制剂的等效范围内。结论:两种氨基葡萄糖制剂生物利用度等效。

Objective： To investigate the bioequivalence of two glucosamine hydrochloride preparations in healthy volunteers. Method： 20 healthy male volunteers were enrolled in a randomized crossover study in which the subjects were randomly assigned to receive single dose of 0. 75 g glucosamine hydrochloride granule （test preparation） or glucosamine hydrochloride capsules （reference preparation）. Plasma concentrations of glucosamine hydrochloride were determined by phthalaldehyde/3-mercaptopropionic acid derivatization puisne LC-MS/MS method. The pharmacokinetic parameters and bioequivalence were calculated with DAS 2. 1.1 software. Result： The main pharmacokinetic parameters of test and reference preparations were as follows：Cmax （1 015 ± 306） and （1 026 ± 470） ng·ml^-1,tmax（2.40 ±1.20） and （2.80 ±1.37） h, t1/2∞ （1. 24 ±0.53） and （1.20 ±0.32） h,AUC0-t（4504±1303） and （4 315 ± 1 410） ng·h·ml^-1 ,AUC0-∞ （4 579 ± 1 275） and （4 341 ± 1 407） ng·h·ml^1. The relative bioavailability of glueosamine hydrochloride granules was （ 114. 1 ± 44. 8 ） %. The 90% confidential intervals （ CI ） of AUC0-t of the test preparation was among the bioequivalent threshold compared with that of the reference preparation. Conclusion： Glucosamine hydrochloride test and reference preparations are bioequivalent.