硫酸氨基葡萄糖胶囊在中国健康人体内的生物等效性试验  

Bioequivalence of glucosamine sulfate capsules after single dose in healthy volunteers

作　　者：杨克旭[1] 荆珊[1] 刘文芳[1] 鲁春艳[1] 王欣 林阳[1] YANG Ke-xu;JING Shan;LIU Wen-fang;LU Chun-yan;WANG Xin;LIN Yang(Bejing Anzhen Hospital,Capial Medical University,Beijing 100029,China;Zhejiang Hisun Pharmaceuical Co.,Ltd.,Taizhou 318000,China)

机构地区：[1]首都医科大学附属北京安贞医院,北京100029 [2]浙江海正药业股份有限公司,台州318000

出　　处：《中国新药杂志》2021年第5期399-402,共4页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项资助项目:心血管疾病药物临床研究示范性平台(2017XZ09304017)。

摘　　要：目的:评价空腹单剂量口服硫酸氨基葡萄糖胶囊受试制剂与参比制剂在中国健康人体中的生物等效性。方法:本研究采用随机、开放、单剂量、三周期、部分重复、三交叉试验设计,共入组健康男性和女性30例,单剂量空腹口服受试制剂和参比制剂硫酸氨基葡萄糖胶囊0.25 g。采用LC-MS/MS测定给药后血浆氨基葡萄糖药物浓度。使用WinNonlin 6.3软件计算非房室模型药动学(PK)参数,采用参比制剂标度的平均生物等效性(RSABE)方法,使用SAS企业版7.1版软件进行等效性评价。结果:经基线校正后的受试制剂和参比制剂中氨基葡萄糖Cmax分别为(585.0±282.2)和(641.0±293.6) ng·mL^(-1),Tmax分别为1.5 h(0.5,5.0 h)和1.5 h(0.5,5.0 h),t1/2分别为(1.8±1.4)和(1.5±0.5) h,AUC0~t分别为(2 089.2±749.5)和(2 298.2±928.4) ng·h·mL^(-1),AUC0~∞分别为(2 095.3±749.7)和(2 303.1±929.0) ng·h·mL^(-1)。受试制剂和参比制剂的AUC0~t,AUC0~∞和Cmax的几何均数比值(受试制剂/参比制剂)的90%置信区间介于拓宽的等效范围74.9%~133.6%和70.1%~142.7%,同时介于未拓宽的等效范围80.0%~125.0%。结论:硫酸氨基葡萄糖胶囊受试制剂与参比制剂在空腹服用的情况下生物等效。Objective: To evaluate the bioequivalence of reference and test formulations of glucosamine sulfate capsules after single dose in healthy Chinese volunteers under fasting condition. Methods: A total of 30 healthy human volunteers participated in a randomized,open,single-dose,three-cycle,partial repeated,three-crossover study. Volunteers were given single dose( 0. 25 g) of tested and reference formulations of glucosamine sulfate capsules under fasting state. Plasma concentration of glucosamine after administration was analyzed by LC-MS/MS method.Non-compartmental pharmacokinetics parameters were calculated by Win Nonlin 6. 3,and bioequivalence was evaluated using reference-scaled average bioequivalence( RSABE) method by SAS 7. 1. Results: For test and reference formulations,Cmax of glucamine( after baseline correction) were( 585. 0 ± 282. 2) and( 641. 0 ± 293. 6) ng·mL^(-1),Tmaxwere 1. 5( 0. 5,5. 0) and 1. 5( 0. 5,5. 0) h,t1/2 were( 1. 8 ± 1. 4) and( 1. 5 ± 0. 5) h,AUC0~twere( 2 089. 2 ±749. 5) and( 2 298. 2 ±928. 4),AUC0 ~ ∞were( 2 095. 3 ± 749. 7) and( 2 303. 1 ± 929. 0),respectively.The geometric mean ratios( GMR) of AUC0~t,AUC0 ~ ∞ and Cmax between test and reference formulations were both within 90% confidence interval broadened bioequivalent rage 74. 9% to 133. 6% and 70. 1% to 142. 7%,and regular bioequivalent range( 80% to 125%). Conclusion: Two formulations were equivalent under fasting condition.

关 键 词：硫酸氨基葡萄糖 高变异药物 内源性药物 生物等效性 参比制剂标度的平均生物等效性 

分 类 号：R969.4[医药卫生—药理学]