Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Diabetes Technol Ther. 2009 Sep;11 Suppl 2:S75-80. doi: 10.1089/dia.2009.0057.
In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects.
Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose.
Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg dose range.
AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.
为了评估与吸入型胰岛素终端使用者相关的药代动力学（PK）和血糖动力学（GD）特征，本研究通过合并不同强度的胶囊，在健康受试者中考察了吸入型胰岛素（AIR）（艾伯维公司，印第安纳波利斯，IN）的暴露量和 GD 效应。
59 名健康、不吸烟的男性或女性受试者，其肺功能正常，入组一项开放标签、随机、交叉研究。受试者接受了多达 5 次的血糖钳夹试验，间隔 5-18 天。所测试的 5 种 AIR 胰岛素治疗包括 1 个 6 单位当量（U-eq）胶囊（含 2.6mg 胰岛素）、3 个 2 U-eq（0.9mg）胶囊（共 2.7mg）、1 个 10 U-eq（3.9mg）胶囊、1 个 6 U-eq 胶囊加 2 个 2 U-eq 胶囊（共 4.4mg）、2 个 10 U-eq 胶囊（共 7.8mg）。给药后最多采集 10 小时的 PK 和 GD 评估样本。
基于 PK（从 0 时间到恢复基线时间和最大浓度的曲线下面积）和 GD（输注的葡萄糖总量和最大葡萄糖输注率）反应，6 U-eq 胶囊给药等效于 3 个 2 U-eq 胶囊；比值的 90%置信区间在（0.8，1.25）区间内。同样，10 U-eq 胶囊给药后的总体暴露量和 GD 反应与 6 U-eq 胶囊加 2 个 2 U-eq 胶囊组合相当。AIR 胰岛素在 2.6-7.8mg 剂量范围内表现出 PK 剂量比例性和 GD 反应的剂量依赖性增加。
在健康受试者中，单次给药后，AIR 胰岛素表现出剂量强度可互换性和剂量比例性。
