Effect of upper respiratory tract infection on AIR inhaled insulin pharmacokinetics and glucodynamics in healthy subjects
Effect of upper respiratory tract infection on AIR inhaled insulin pharmacokinetics and glucodynamics in healthy subjects
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DOI：
10.1038/sj.clpt.6100286
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发表时间：
2008-02-01
影响因子：
6.7
通讯作者：
Busse, W. W.
中科院分区：
文献类型：
--
作者：
Gern, J. E.;Stone, C. K.;Busse, W. W.
尚未确定在急性上呼吸道感染（URI）期间使用AIR吸入胰岛素（AIR Insulin; AIR是Alkermes的注册商标）的适用性。21例健康、非糖尿病受试者入组了一项单序列、两阶段、正葡萄糖钳夹研究。受试者在鼻病毒（RV 16）接种前和症状性感染期间接受了12 U当量剂量的AIR胰岛素单次给药。肺功能测定用于评价肺安全性。AIR胰岛素暴露（从时间0至IRI浓度恢复至给药前基线值的免疫反应性胰岛素（IRI）浓度-时间曲线下面积（AUC（0-t '）和葡萄糖动力学反应（输注的葡萄糖总量（G（tot）在RV感染之前和期间相当（AUC（0-t'）46，300 vs 52，600 pmol min/l，P=0.21; G（tot）61，800 vs 68，700 mg，P=0.42）。在URI期间，药代动力学和药效学参数的变异性没有改变;不良事件的数量或强度也没有改变。在AIR胰岛素给药后或URI期间，未观察到用力呼气量或用力肺活量的显著变化。AIR Insulin系统在实验诱导的RV感染条件下提供类似的药代动力学和葡萄糖动力学反应，被认为适合在URI期间用于糖尿病患者。
The suitability of employing AIR Inhaled Insulin (AIR Insulin; AIR is a registered trademark of Alkermes) during acute upper respiratory tract infection (URI) has not been determined. Twenty-one healthy, non-diabetic subjects were enrolled in a single-sequence, two-period, euglycemic clamp study. Subjects received a single 12 U-equivalent dose of AIR Insulin before rhinovirus (RV16) inoculation and during symptomatic infection. Spirometry was used to evaluate pulmonary safety. AIR Insulin exposure (the area under the immunoreactive insulin (IRI) concentration vs time curve from time zero until the IRI concentrations returned to the predose baseline value (AUC(0-t'))) and glucodynamic response (total amount of glucose infused (G(tot))) were comparable before and during RV infection (AUC(0-t') 46,300 vs 52,600 pmol min/l, P=0.21; G(tot) 61,800 vs 68,700 mg, P=0.42, respectively). Variability of pharmacokinetic and pharmacodynamic parameters did not change during URI; either did the number or intensity of adverse events. No significant change in forced expiratory volume or forced vital capacity was observed following AIR Insulin administration or during URI. The AIR Insulin system provides similar pharmacokinetic and glucodynamic responses under conditions of an experimentally induced RV infection and is regarded as suitable for use in diabetic patients during URIs.