Diurnal Ltd, Cardiff, UK.
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
Drug Deliv Transl Res. 2023 Jan;13(1):1-8. doi: 10.1007/s13346-022-01183-w. Epub 2022 May 26.
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.
在这封鼓舞人心的信中，我们描述了内分泌时间治疗学的发展，以恢复重要的应激激素皮质醇的生理节律。面临的挑战包括证明药物靶点的昼夜节律，创建一种能够复制该节律的药物配方，然后在临床试验中证明其益处。皮质醇的生理昼夜节律定义明确，醒来时皮质醇水平高，入睡时皮质醇水平低。我们尝试了不同的制剂技术，包括控释片和多颗粒制剂，以在疾病导致的情况下复制皮质醇节律。我们描述了 Efmody 的开发，这是一种氢化可的松的控释制剂，可复制皮质醇的昼夜节律，并改善最常见的遗传性肾上腺皮质功能不全——先天性肾上腺增生症的疾病控制。该计划表明，通过控释技术，有可能用生理性替代治疗来治疗慢性内分泌疾病，以保持终生健康。
