Strack Thomas
Takeda Global Research and Development, 675 North Field Drive, Lake Forest, IL 60045, USA.
Curr Opin Investig Drugs. 2010 Apr;11(4):394-401.
Limited progress has been made toward developing safer and more acceptable methods for the administration of insulin treatment, despite several attempts to replace subcutaneous injection with alternate routes of administration. Attempts to develop methods for pulmonary administration have demonstrated promise, but have been met with little patient acceptance thus far, while potentially more attractive routes, such as nasal, oral or transdermal administration, have been mainly unsuccessful in providing sufficiently favorable pharmacokinetics and bioavailability for clinical use. The use of enhancers and/or enzyme inhibitors transiently increases absorption across the epithelia of the oral and nasal cavities and the mucosa of the gastrointestinal tract; however, absorption appears to be highly variable, overall bioavailability remains low, causing the cost of goods to be high, and the long-term safety of additives and insulin as a potential local growth factor is not well characterized. While research in some areas of alternative insulin delivery is ongoing, the continued refinement of subcutaneous injection devices and new pharmacological strategies for patients with type 2 diabetes may reduce the need for delivering exogenous insulin and, thus, for alternate administration routes.
尽管多次尝试用其他给药途径替代皮下注射，但在开发更安全、更易接受的胰岛素治疗给药方法方面进展有限。开发肺部给药方法的尝试已显示出前景，但迄今为止患者接受度不高，而诸如鼻腔、口服或透皮给药等可能更具吸引力的途径，在提供足够良好的药代动力学和生物利用度以用于临床方面，主要未获成功。使用增强剂和/或酶抑制剂可暂时增加口腔和鼻腔上皮以及胃肠道黏膜的吸收；然而，吸收似乎高度可变，总体生物利用度仍然较低，导致商品成本高昂，而且添加剂和胰岛素作为潜在局部生长因子的长期安全性尚不明确。虽然替代胰岛素给药某些领域的研究仍在进行，但2型糖尿病患者皮下注射装置的持续改进和新的药理学策略可能会减少外源性胰岛素的给药需求，从而减少对替代给药途径的需求。
