Piazzola Cecilia, Castinetti Frederic, von Fabeck Katharina, Simon Nicolas
INSERM, MMG, Department of Endocrinology, La Conception Hospital, Assistance Publique Hopitaux de Marseille, Aix Marseille University, Marseille, France.
INSERM, IRD, SESSTIM, Sainte Marguerite Hospital, Clinical Pharmacology and Poison Control Centre, Aix Marseille University, Marseille, France.
Eur J Endocrinol. 2025 Sep 30;193(4):K11-K15. doi: 10.1093/ejendo/lvaf185.
Over the past 10 years, osilodrostat has become one of the most commonly used steroidogenesis inhibitors in patients with Cushing's syndrome. The starting dose is usually determined based on the product characteristics, the prescriber's experience, and cortisol levels. However, no study has attempted to determine whether there was a dose-response relationship between osilodrostat and cortisol reduction. In this study, we developed a preliminary kinetic-pharmacodynamic model to tailor osilodrostat in patients with Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome. We first analyzed the decrease in cortisol 48 hours after initiation or dose change of osilodrostat in 18 patients. Simulations were then performed for different doses of osilodrostat to evaluate the variation in cortisol concentrations. Our results report the first dose-response relationship between osilodrostat dose and cortisol levels, which should be helpful in identifying the optimal dosing regimen in patients with Cushing's syndrome and in individualizing treatment to approximate a nychthemeral rhythm.
在过去10年里，奥西卓司他已成为库欣综合征患者中最常用的类固醇生成抑制剂之一。起始剂量通常根据产品特性、处方医生的经验和皮质醇水平来确定。然而，尚无研究试图确定奥西卓司他与皮质醇降低之间是否存在剂量反应关系。在本研究中，我们建立了一个初步的动力学-药效学模型，以调整奥西卓司他在促肾上腺皮质激素（ACTH）依赖性库欣综合征患者中的应用。我们首先分析了18例患者在开始使用奥西卓司他或改变剂量后48小时皮质醇的下降情况。然后对不同剂量的奥西卓司他进行模拟，以评估皮质醇浓度的变化。我们的结果首次报道了奥西卓司他剂量与皮质醇水平之间的剂量反应关系，这将有助于确定库欣综合征患者的最佳给药方案，并使治疗个体化以接近昼夜节律。
