Morley Paul
Zelos Therapeutics, Inc., Ottawa, Ontario K1G 5L1, Canada.
Expert Opin Drug Deliv. 2005 Nov;2(6):993-1002. doi: 10.1517/17425247.2.6.993.
Parathyroid hormone (PTH), along with its fragments and analogues, potently restores bone mass and biomechanical strength in animal models of osteoporosis, and reduces fractures by up to 65% in clinical trials in osteoporotic patients. Despite this demonstrated efficacy, patient acceptance and compliance with PTH is limited by the need for daily subcutaneous injections. The development of an equally efficacious, noninjectable form of PTH would significantly expand the present market. A challenge to the development of an alternative delivery system is the requirement for low-dose, daily, intermittent pulses of PTH to induce the anabolic actions on bone. In this review, recent basic and clinical efforts to deliver PTH by oral, buccal, sublingual, transdermal, nasal and pulmonary approaches will be addressed.
甲状旁腺激素（PTH）及其片段和类似物，在骨质疏松动物模型中能有效恢复骨量和生物力学强度，在骨质疏松患者的临床试验中可将骨折发生率降低多达65%。尽管有如此显著的疗效，但由于需要每日皮下注射，患者对PTH的接受度和依从性受到限制。开发一种同样有效的、非注射形式的PTH将显著扩大当前市场。开发替代给药系统面临的一个挑战是需要低剂量、每日、间歇性的PTH脉冲来诱导对骨骼的合成代谢作用。在这篇综述中，将探讨近期通过口服、颊部、舌下、经皮、鼻腔和肺部途径递送PTH的基础和临床研究成果。
