In this inspirational note, we describe the development of an endocrine chronotherapy to restore the physiological rhythm of the essential adrenal stress hormone, cortisol. The challenges included demonstrating the circadian rhythm of the drug target, creating a drug formulation that replicated that rhythm and then proving benefit in clinical trials. The physiological cortisol circadian rhythm is well defined with cortisol levels high on waking and low on going to sleep. We experimented with different formulation technologies including modified-release tablets and multi-particulates to replicate the cortisol rhythm where absent through disease. We describe the development of Efmody^®, a modified-release formulation of hydrocortisone, which replicates the cortisol diurnal rhythm and improves the disease control of congenital adrenal hyperplasia, the commonest hereditary form of adrenal insufficiency. This program shows it is possible, through modified-release technology, to treat chronic endocrine diseases with physiological replacement to preserve health for life.

在这篇鼓舞人心的文章中，我们描述了内分泌时间疗法的发展，以恢复基本肾上腺应激激素皮质醇的生理节律。挑战包括展示药物靶标的昼夜节律，创建复制该节律的药物制剂，然后在临床试验中证明其益处。生理皮质醇昼夜节律明确定义为皮质醇水平在清醒时高而在入睡时低。我们试验了不同的制剂技术，包括缓释片剂和多颗粒，以复制因疾病而缺失的皮质醇节律。我们描述了 Efmody ^®的开发，一种氢化可的松的改良释放制剂，它复制皮质醇的昼夜节律并改善先天性肾上腺增生的疾病控制，这是肾上腺功能不全的最常见遗传形式。该项目表明，通过缓释技术，可以通过生理替代治疗慢性内分泌疾病，实现终生健康。