Pfützner Andreas, Mann Alfred E, Steiner Solomon S
Pharmaceutical Discovery Corporation, A MannKind Company, Danbury, Connecticut, USA.
Diabetes Technol Ther. 2002;4(5):589-94. doi: 10.1089/152091502320798204.
The development of pulmonary insulin formulation offers an attractive alternative to the current requirement of repeated subcutaneous (s.c.) injections for insulin administration. Technosphere/Insulin is a formulation of regular human insulin that was designed to produce an efficient transport of insulin across the respiratory epithelium into the systemic circulation. Several studies using the euglycemic clamp technique were performed in healthy volunteers and patients with Type 2 diabetes to assess the pharmacokinetic and pharmacodynamic properties of Technosphere/Insulin. The investigations revealed a very rapid systemic insulin uptake (insulin T(max) approximately 12-14 min), a fast onset of action (maximum activity approximately 20-30 min), and a short duration of action (approximately 2-3 h) in healthy volunteers and in patients with Type 2 diabetes. In the first study, employing a commercially available inhaler, the relative bioavailability (compared with s.c. injections) was initially reported to be 26% for the first 3 h and 16% for the entire observation period of 6 h. With the development of a specific inhaler adapted to the physical properties of Technosphere/Insulin, the MedTone Inhaler, relative bioavailability was 50% for the first 3 h and 30% over the entire 6-h period. A clear linearity of systemic insulin uptake was observed in a study employing 12 healthy volunteers inhaling doses of 25, 50, and 100 IU. Repeated inhalation of 100 IU of Technosphere/Insulin by 12 patients with Type 2 diabetes revealed a lower variability in comparison with published s.c. injection data from healthy volunteers. This new Technosphere/Insulin formulation was well tolerated, and no serious adverse events were reported in any of the investigations. Given its attractive time-action profile, Technosphere/Insulin may become a suitable alternative to s.c. injection for prandial insulin delivery, especially in patients with Type 2 diabetes, if the long-term safety, tolerability, and efficacy of this pulmonary insulin are established and confirmed in future studies.
肺部胰岛素制剂的研发为目前胰岛素给药所需的重复皮下注射提供了一种有吸引力的替代方法。Technosphere/胰岛素是一种常规人胰岛素制剂，其设计目的是使胰岛素有效穿过呼吸道上皮进入体循环。在健康志愿者和2型糖尿病患者中进行了多项使用正常血糖钳夹技术的研究，以评估Technosphere/胰岛素的药代动力学和药效学特性。研究发现，在健康志愿者和2型糖尿病患者中，胰岛素的全身摄取非常迅速（胰岛素达峰时间约为12 - 14分钟），起效快（最大活性约为20 - 30分钟），作用持续时间短（约2 - 3小时）。在第一项研究中，使用市售吸入器，最初报告在前3小时相对生物利用度（与皮下注射相比）为26%，在整个6小时观察期内为16%。随着适应Technosphere/胰岛素物理性质的特定吸入器——MedTone吸入器的研发，前3小时相对生物利用度为50%，在整个6小时期间为30%。在一项对12名健康志愿者吸入25、50和100国际单位剂量的研究中，观察到全身胰岛素摄取呈明显的线性关系。12名2型糖尿病患者重复吸入100国际单位的Technosphere/胰岛素，与健康志愿者已发表的皮下注射数据相比，变异性较低。这种新的Technosphere/胰岛素制剂耐受性良好，在任何研究中均未报告严重不良事件。鉴于其具有吸引力的时间 - 作用曲线，如果这种肺部胰岛素的长期安全性、耐受性和疗效在未来研究中得到确立和证实，Technosphere/胰岛素可能成为餐时胰岛素给药皮下注射的合适替代方法，尤其是在2型糖尿病患者中。
