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目的以正规胰岛素皮下注射制剂为参比,进行胰岛素肠溶胶丸人体药代动力学、药效动力学及相对生物利用度研究。方法 20例健康受试者,男14例,女6例,年龄21～41(28.6±5.2)岁,BMI 18.0～22.0(21.2±1.1)kg/m~2,在正常血糖葡萄糖钳夹技术平台上,按随机顺序分别接受受试制剂(50 IU)和参比制剂(15 IU)两次试验。每个试验日经2h 平衡后给药,采29个时点血样测血清胰岛素水平,同时记录12h 中每5分钟的葡萄糖输注率,以计算药代动力学和药效动力学参数。结果受试制剂与参比制剂的血药浓度峰值分别为(22.1±8.0)mIU/L 和(118.6±25.2)mIU/L,达峰时间分别为(255.8±142.2)min 和(115.5±43.4)min。葡萄糖处置率峰值(GIRmax)分别为(3.56±0.85)mg·kg~(-1)·min~(-1)和(4.87±1.26)mg·kg~(-1)·min~(-1),GIRmax 达峰时间分别为(166.3±75.9)min 和(148.0±40.8)min。受试制剂相对生物利用度为(7.42±3.25)%,相对有效性为(24.78±0.08)%。结论胰岛素肠溶胶丸可经胃肠道吸收入血,相对生物利用度与相对有效性差别大,充分体现了口服胰岛素制剂模拟内源胰岛素分泌生理过程所带来的益处。其药代、药效特点为进一步临床研究提供可靠的依据。
OBJECTIVE To study the pharmacokinetics, pharmacodynamics and relative bioavailability of insulin enteric-coated gels with reference to regular insulin subcutaneous injection. Methods Twenty healthy subjects, 14 males and 6 females, aged from 21 to 41 years (28.6 ± 5.2) years and BMI ranged from 18.0 to 22.0 (21.2 ± 1.1) kg / m 2, were included in the study. Two trials of the test preparation (50 IU) and the reference preparation (15 IU) were performed in random order. Each test day after 2h administration, blood samples taken at 29 o’clock serum insulin levels, while recording every 12h glucose infusion rate every 5 minutes to calculate the pharmacokinetic and pharmacodynamic parameters. Results The peak plasma concentrations of test and reference preparations were (22.1 ± 8.0) mIU / L and (118.6 ± 25.2) mIU / L, respectively, reaching peak values of (255.8 ± 142.2) min and (115.5 ± 43.4) min. The peak glucose concentration (GIRmax) were (3.56 ± 0.85) mg · kg -1 · min -1 and 4.87 ± 1.26 mg · kg -1 · min -1, respectively , Peak time of GIRmax were (166.3 ± 75.9) min and (148.0 ± 40.8) min, respectively. The relative bioavailability of the test preparation was (7.42 ± 3.25)%, the relative effectiveness was (24.78 ± 0.08)%. Conclusion Insulin enteric-coated capsules can be absorbed into the bloodstream through the gastrointestinal tract. The relative bioavailability and relative effectiveness vary greatly, which fully reflects the benefits of oral insulin preparations in mimicking the physiological process of endogenous insulin secretion. Its pharmacokinetics and pharmacodynamic characteristics provide a reliable basis for further clinical research.