Rodríguez-Fernández Karine, Zarzoso-Foj Javier, Saez-Bello Marina, Mateu-Puchades Almudena, Martorell-Calatayud Antonio, Merino-Sanjuan Matilde, Gras-Colomer Elena, Climente-Martí Monica, Mangas-Sanjuan Victor
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain.
Interuniversity Research Institute for Molecular Recognition and Technological Development, Polytechnic University of Valencia-University of Valencia, 46100 Valencia, Spain.
Pharmaceutics. 2024 Oct 4;16(10):1295. doi: 10.3390/pharmaceutics16101295.
BACKGROUND/OBJECTIVES: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting clinical dose selection decisions.
This study proposes a methodology to individualize ustekinumab (UTK) dosing strategies for 23 Spanish patients with moderate to severe chronic plaque psoriasis., considering the uncertainty of individual parameters within a population PK/PD model.
An indirect response model from previous research was used to describe the PK/PD relationship between UTK serum concentrations and the Psoriasis Area and Severity Index (PASI) score. A maximum inhibition drug effect (I) model was selected, and a first-order remission constant rate of psoriatic skin lesion (k = 0.016 d) was estimated.
The MIPD approach predicted that 35% and 26% of the patients would need an optimized and intensified dosage regimen, respectively, compared to the regimen typically used in clinical practice. This analysis demonstrated its utility as a tool for selecting personalized UTK dosing regimens in clinical practice in order to optimize the probability of achieving targeted clinical outcomes in patients with psoriasis.
背景/目的：实施由群体药代动力学/药效学（PK/PD）模型指导的模型 informed 精准给药（MIPD）策略可以加强对银屑病等炎症性疾病的管理。然而，MIPD 过程中收集的个体实验数据的程度显著影响估计个体 PK/PD 参数的不确定性，从而影响临床剂量选择决策。
本研究提出了一种方法，用于为 23 名西班牙中重度慢性斑块状银屑病患者个体化制定优特克单抗（UTK）给药策略，同时考虑群体 PK/PD 模型中个体参数的不确定性。
使用先前研究中的间接反应模型来描述 UTK 血清浓度与银屑病面积和严重程度指数（PASI）评分之间的 PK/PD 关系。选择了最大抑制药物效应（I）模型，并估计了银屑病皮损的一级缓解恒定速率（k = 0.016 d）。
与临床实践中通常使用的方案相比，MIPD 方法预测分别有 35%和 26%的患者需要优化和强化的给药方案。该分析证明了其作为临床实践中选择个性化 UTK 给药方案的工具的效用，以便优化银屑病患者实现靶向临床结果的概率。
