常规型重组人胰岛素重和林TMR的人体药代动力学、药效动力学及生物等效性

Pharmacokinetics, pharmacodynamics, and bioequivalence study of SciLin TMR recombinant human insulin injection preparation

目的在中国健康受试者中，进行常规型重组人胰岛索重和林TMR和优泌林0R的人体药代动力学、药效动力学研究，并评价两种制剂的生物等效性。方法本研究为阳性对照、单次剂量、开放标签、随机、交叉研究。2007年3月至0月招募20名男性健康受试者分别在2个试验日接受试验观察，2次试验间隔时间为7—14d。受试者按随机数字表法随机分为2组，一组第1次用重和林TMR，第2次用优泌林R；另一组则第1次用优泌林R，第2次用重和林TMR。采用正常血糖葡萄糖钳夹技术平台进行药代动力学和药效动力学研究。结果重和林。”R和优泌林@R比较，药代动力学达峰时间[（105．8±19．1）rain比（103．5±18．1）min，P=0．389]和药效动力学峰效时间[（132．8±16．8）min比（132．8±18．6）min，P=0．697]差异均无统计学意义。重和林TMR的相对生物利用度为（102．2±7．6）％，相对生物有效性为（107．4±18．8）％。重和林TMR的药代动力学参数血胰岛素峰浓度和0—10h的血胰岛素浓度曲线下面积90％可信区间分别为99．32％～102．62％（等效范围70％～143％）和98．98％～104．99％（等效范围80％-125％），药效动力学参数最高葡萄糖输注率、0～10h葡萄糖输注率曲线下面积90％可信区间分别为97．36％-103．49％（等效范围70％～143％）和98．72％～113．54％（等效范围80％-125％），两种制剂具有生物等效性。试验前、后各安全性指标均无临床意义的异常值。试验过程中未见有低血糖、过敏反应及注射局部不良反应发生。结论受试制剂重和林TMR和参比制剂优泌林R具有生物等效性。

Objective To study the pharmacokinetics and pharmacodynamics of recombinant human insulin preparations SciLin TMR and Humulin R, and to evaluate their bioequivalence in Chinese healthy vol- unteers. Methods In this positive control, single dose, open label, randomized cross-over study, 20 male healthy volunteers were recruited from March to October 2007, and tested on two experimental days with an in- terval of 7 - 14 days. The volunteers were divided into two groups with a random number table, one group was in- jected with SciLin TMR for the first time and Humulin R for the second time, the other group was injected with the opposite. The pharmacokinetics and pharmacodynamic properties were evaluated by euglycemic glucose clamp study. Results Time to peak concentration [ Tmax （ 105.8 ± 19.1 ） minutes vs. （ 103.5 ± 18.1 ） minutes, P = 0.389） and time to maximum glucose infusion rate [ Tmax （132.8 ± 16.8 ）minutes vs. （132.8 ± 18.6）minutes, P = 0. 697 ] for SciLin TMR and Humulin R were similar. The relative bioavailability of SciLin TMR was （ 102.2 ±7.6） %, and the relative biological effectiveness was （ 107.4 ± 18.8） %. The 90% confidence inter- val（Cl） of peak concentration（ Cmax ） and area under the curve of blood glucose concentration at 0 - 10 hours （AUCIns0-10 ） of SciLin TMR were 99.32% - 102.62% （equivalent range 70% - 143% ） and 98.98% - 104.99% （equivalent range 80% -125% ）, respectively; 90% C1 of the maximum glucose infusion rate（ GIRm,x ） and AUCCIR 0-10 were 97.36% - 103.49% （ equivalent range 70% - 143% ） and 98.72% - 113.54% （ equivalent range 80% - 125% ）, respectively, indicating that SciLin TMR and Humulin R was bioequivalent. There was no clinically significant abnormalities in the safety indexes before and after the tests. During the trial, no hypoglycemie events, allergic reactions, or local injection adverse reaction occurred. Conclusion The studied recombinant human insulin preparation SeiLin TMR may be bioequivalent as Humulin R.