国产甘精胰岛素注射液在比格犬体内的生物等效性评价

摘要

Objective To evaluate the pharmacokinetics and bioequivalence of domestic and imported insulin glargine injections in Beagle dogs. Methods Beagle dogs were given double dose subcutaneous administration of the test preparation and the reference preparation itself, blood samples were collected at different time points after intravenous blood samples, and the blood glucose levels were determined by Roche Glucose meter synchronously. RIA method can detect blood concentration, calculation of pharmacokinetics parameters by using the DAS 2. 2 software and SPSS 17. 0 for statistical analysis. Results Beagle' s dogs were treated with test preparation and reference preparation following sc administration at the dose of double dose. The main pharmacokinetic parameters of test preparation(4 U) and reference preparation(4 U) were as following; the elimination half-life (t1/2) was (4. 52±3.62) and (3. 42 ±2. 97) h, the peak concentration (Cmax) was (102.0±41.8) and (94. 3 ±42. 3) μU/ml, the peak time (Tmax) was (2. 670 ± 0. 651) and (3. 000 ±0. 853) h,and the area under the concentration-time curve (AUC0-t) was (655 ±276) and (610 ± 197) μU/(ml · h),individually. Respectively, the minimum blood glucose levels (Cmin) of the tested and referenced samples were (1. 620 ± 0. 335 ) and (1. 530 ± 0. 377 ) mmol/L, and the Tmin(time to reach minimumblood glucose level) was (3. 83 ± 1. 19) and (3. 75 ± 1. 42) h, respectively. 8 U of the tU2 was (3. 36 ± 1. 89) and (3. 16 ±1. 62) h, the Cmax was (135.0 ±57.7) and (133.0 ± 54.3) μU/ml, Tmax was (3. 83 ± 1. 27) and (3. 750 ±0. 866) h, and the AUC0-t was (920 ± 274) and (941 ±250) μU/(ml · h), individually. What's more, the Cmin of the tested and referenced samples were (1. 590 ±0. 355) and(1. 570 ±0. 281) mmol/L, respectively, and the Tmin was (6. 33 ± 1. 37) and (5. 92 ± 1. 68) h separately. Conclusion Domestic insulin glargine injection and control agent (Lantus?)has a bioequivalence.%目的 探究国内生产的甘精胰岛素注射剂与国外同类型制剂在比格犬体内是否具有生物等效性.方法 采用比格犬双剂量(4 U/只和8 U/只)自身双交叉皮下给药方案,在不同时间点经前腿静脉测定血糖水平,同时收集血样于抗凝管中,放射免疫分析法测定外源性胰岛素浓度;药代动力学参数的计算采用DAS 2. 2,SPSS 17.0进行统计学检验,并分析其生物等效性.结果 比格犬(12只)交叉皮下注射T制剂与R制剂(4 U/只)后,计算得到的外源性胰岛素浓度的主要药代动力学参数分别为:t1/2(平均)为(4.52 ± 3.62)、(3.42±2.97) h.AUC0-1(平均)为(655 ±276)、(610± 197) μU/(ml · h),Cmax(平均) 为(102.0 ±41.8) 、(94.3 ± 42.3) μU/ml, Tmax(平均)为(2.670±0.651)、(3.000±0.853) h;血糖值Tmin(平均)分别为(3.83±1.19)、(3.75±1.42) h;血糖 Cmin(平均)为(1. 620 ± 0. 335) mmol/L 和(1. 530 ± 0. 377) mmol/L.比格犬(12只)交叉注射T制剂与R制剂(8 U/只)后,计算得到的外源性胰岛素浓度主要药代动力学参数分别是:Cmax(平均)为(135. 0 ± 57. 7)、(133. 0 ± 54. 3) μU/ml, AUC0-1(平均)为(920 ± 274)、(941 ± 250) μU/(ml · h), t1/2(平均)为(3. 36 ± 1. 89)、(3. 16 ± 1. 62) h, Tmax(平均)为(3. 83±1.27),(3. 750 ±0. 866) h;两个制剂的血糖值Tmin(平均)为(6. 33 ± 1. 37)、(5. 92 ± 1. 68) h, Cmin(平均) 为(1. 590 ± 0. 355)、(1.570 ±0.281) mmol/L.结论 国产的重组甘精胰岛素注射制剂与国外上市制剂(来得时?)具有相同的生物等效性.