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目的与皮下注射正规胰岛素制剂比较,研究胰岛素粉雾剂人体药代动力学及药效动力学特征及其相对生物利用度。方法18名健康受试者(男14名,女4名),平均年龄(24.9±1.7)岁(21～33岁),体重指数为(20.6±1.2)kg/m~2(18.2～23.0 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吸入胰岛素粉雾剂(80 U)和皮下注射正规胰岛素(15 U)两次试验。于给药后0、20、30、40、50、60、70、80、90、100、110、120、135、150、165、180、195、210、225、240、270、300、330、360、390、420、450、480 min取血测血清胰岛素水平,同时记录8 h中每5 min的葡萄糖输注率,以计算药代动力学和药效动力学参数。结果受试制剂胰岛素粉雾剂及参比制剂皮下注射正规胰岛素的血药浓度峰值C_(max)分别为(57.9±17.8)和(114.5±29.7)mU/L,达峰时间T_(max)为(46.7±45.6)和(107.8±33.7)min。葡萄糖处置率峰值GIR_(max)为(3.35±0.98)和(5.17±1.75)mg·kg~(-1)·min~(-1),其达峰时间T_(GIRmax)为(88.3±17.0)和(151.9±34.6)min。相对生物利用度为(10.26±2.25)%,相对生物有效性为(14.33±7.26)%。结论胰岛素粉雾剂可经肺吸收入血,其吸收及降糖作用均较皮下注射正规胰岛素快。其药代、药效特点为进一步临床研究提供可靠的依据。
OBJECTIVE To compare the pharmacokinetics, pharmacodynamics and relative bioavailability of insulin powder aerosol with regular insulin preparations. Methods Eighteen healthy subjects (14 males and 4 females) with a mean age of 24.9 ± 1.7 years (21-33 years) and body mass index (BMI) of 20.6 ± 1.2 kg / m 2 (18.2-23.0 kg / m ~ 2) on the platform of the normal glucose glucose clamp technology, two tests of inhalation of insulin powder aerosol (80 U) and subcutaneous injection of regular insulin (15 U) were conducted in random order. 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 270, 300, 330, 360,390,420,450,480 min blood test serum insulin levels, and 8 h in every 5 min glucose infusion rate to calculate the pharmacokinetics and pharmacodynamics parameters. Results The plasma C max values of subcutaneous insulin injections and reference preparations were (57.9 ± 17.8) and (114.5 ± 29.7) mU / L, respectively. The peak time T max was (46.7 ± 45.6) and (107.8 ± 33.7) min, respectively. The peak GIRmax of glucose was (3.35 ± 0.98) and (5.17 ± 1.75) mg · kg -1 · min -1, and the peak time of GIRmax was (88.3 ± 17.0) And (151.9 ± 34.6) min. The relative bioavailability was (10.26 ± 2.25)% and the relative bioavailability was (14.33 ± 7.26)%. Conclusion Insulin powder aerosol can be absorbed into the bloodstream through the lungs and its absorption and hypoglycemic effects are faster than that of regular insulin injected subcutaneously. Its pharmacokinetics and pharmacodynamic characteristics provide a reliable basis for further clinical research.