单次空腹皮下注射那屈肝素钙注射液在中国健康受试者的生物等效性研究  

Bioequivalence of nadroparin calcium injection in Chinese healthy volunteers by single subcutaneous injection fasting under fasting condition

作　　者：钱亚琴 曲清 范金华 QIAN Ya-qin;QU Qing;FAN Jin-hua(Department of Pharmaceutical,Nanjing Mochou Vocational School,Nanjing 210017,Jiangsu Province,China;Nanjing King-friend Biochemical Pharmaceutical Co.,Ltd.,Nanjing 210061,Jiangsu Province,China;Phase I Clinical Trial Center,Henan(Zhengzhou)Zhonghui Cardiovascular Hospital,Zhengzhou 450006,Henan Province,China)

机构地区：[1]南京市莫愁中等专业学校药学系,江苏南京210017 [2]南京健友生化制药股份有限公司,江苏南京210061 [3]河南(郑州)中汇心血管病医院Ⅰ期临床研究中心,河南郑州450006

出　　处：《中国临床药理学杂志》2020年第13期1875-1878,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的比较南京健友生化制药股份有限公司(受试制剂)和Glaxo Wellcome Production(参比制剂)生产的那屈肝素钙注射液在中国健康受试者单次空腹皮下注射给药后的生物等效性。方法按单剂量、开放、随机、双周期交叉设计。将24例健康受试者随机分2组,洗脱期7 d,分别在2个周期交叉单次空腹皮下注射那屈肝素钙注射液受试制剂或参比制剂0.6 mL/6150 U,用发色底物法测定人血浆中抗Xa因子活性及血浆中抗Ⅱa因子活性,用WinNonlin7.0软件按非房室模型计算药代动力学参数,并进行生物等效性评价。结果单剂量空腹皮下注射受试和参比制剂后,血浆抗Xa因子的主要药代动力学参数如下:t1/2分别为(4.14±1.31)和(4.44±1.82)h,tmax分别为6.00(2.50,8.00)和5.50(2.00,7.00)h,Cmax-Anti-Ⅹa分别为(0.53±0.12)和(0.53±0.12)U·mL^-1,受试制剂与参比制剂抗Xa因子的AUEC0~t、AUEC0~∞和Cmax-Anti-Ⅹa的90%置信区间分别为96.41%~101.90%,93.80%~101.45%和97.12%~107.06%;血浆抗Ⅱa因子的主要药代动力学参数如下:t1/2分别为(10.55±7.93)和(8.95±6.32)h,tmax分别为4.00(2.50,8.00)和4.00(2.00,7.00)h,Cmax-Anti-Ⅱa分别为(0.06±0.02)和(0.07±0.02)U·mL^-1。结论单次空腹皮下注射受试制剂与参比制剂在中国健康受试者体内具有生物等效性。Objective To evaluate the relative bioavailability of nadroparin calcium injection produced by Nanjing King-friend biochemical pharmaceutical Co.LTD(tested preparation)and nadroparin calcium injection produced by Glaxo Wellcome Production(reference preparation)after single fasting subcutaneous injection in Chinese healthy volunteers.Methods According to a single-dose,open-label,randomized,two-period crossover design,twenty-four healthy volunteers were randomly divided into two groups,then a single fasting subcutaneous injection dose 0.6 mL/6150 U of nadroparin calcium injection of the test preparation and reference preparation was given to respectively in two periods in a crossover way with a washout period of 7 days.The activity of anti-Xa and anti-Ⅱa in human plasma were determined by the method of certified chromogenic substrate.The pharmacokinetic parameters were calculated according to the non-compartment model by WinNonlin 7.0 and the bioequivalence was evaluated.Results The main pharmacokinetic parameters of plasma anti-Xa after a single subcutaneous injection of test preparation and reference preparation were as follows:t1/2 were(4.14±1.31)and(4.44±1.82)h,tmaxwere6.00(2.50,8.00)and 5.50(2.00,7.00)h,Cmax-Anti-Ⅹa were(0.53±0.12)and(0.53±0.12)U·mL^-1.The 90%CI of AUEC0-t,AUEC0-∞and Cmax-Anti-Ⅹa for Anti-Xa activity were 96.41%-101.90%,93.80%-101.45%,97.12%-107.06%,respectively.The main pharmacokinetic parameters of plasma anti-Ⅱa were as follows:t1/2 were(10.55±7.93)and(8.95±6.32)h,tmaxwere 4.00(2.50,8.00)and 4.00(2.00,7.00)h,Cmax-Anti-Ⅱa were(0.06±0.02)and(0.07±0.02)U·mL^-1.Conclusion The results of single fasting subcutaneous administration showed that the tested and reference preparations were bioequivalent in Chinese healthy volunteers.

关 键 词：那屈肝素钙注射液 发色底物法 生物等效性 药代动力学 

分 类 号：R973.2[医药卫生—药品]