Physiologically-based pharmacokinetic modeling to predict the exposure and provide dosage regimens of adalimumab in patients with juvenile idiopathic arthritis.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Expert Review of Clinical Pharmacology Pub Date : 2025-05-12 DOI:10.1080/17512433.2025.2502366

Ya-Xin Liu, Li-Ying Gong, Jin-Long Liu, Qi Pei, Yun Kuang, Guo-Ping Yang

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引用次数: 0

Abstract

Background: Adalimumab has been approved for treating juvenile idiopathic arthritis (JIA). This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model for adalimumab in JIA patients to optimize personalized treatment.

Methods: A comprehensive literature search identified 13 clinical studies as the dataset for constructing and validating a PBPK model of adalimumab. Initially, a PBPK model for adalimumab in adults was constructed using PK-Sim and Mobi software. Subsequently, virtual pediatric populations were created by incorporating age-dependent parameters from the PK-Sim database, extending the model to JIA patients. Finally, based on the developed PBPK model for adalimumab in JIA patients, dosing regimens were evaluated for different age groups.

Results: This study successfully developed and validated a PBPK model for adalimumab in both adult and pediatric populations. The model for adults accurately predicted 92.90% of the concentrations within 0.5-2 times the observed values, while the pediatric model predicted 90.62% of the concentrations within 0.5-2-fold range. For pediatric patients with JIA, age- and weight-based dosing is recommended to achieve trough concentrations comparable to those in adults.

Conclusion: A PBPK model for adalimumab in pediatric patients with JIA was developed, providing a basis for personalized dosing regimens in this population.

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基于生理的药代动力学模型预测阿达木单抗在幼年特发性关节炎患者中的暴露并提供剂量方案。

背景：阿达木单抗已被批准用于治疗青少年特发性关节炎（JIA）。本研究旨在建立阿达木单抗在JIA患者中的基于生理的药代动力学（PBPK）模型，以优化个性化治疗。方法：全面的文献检索确定了13项临床研究作为构建和验证阿达木单抗PBPK模型的数据集。最初，使用PK-Sim和Mobi软件构建成人阿达木单抗的PBPK模型。随后，通过结合PK-Sim数据库中的年龄相关参数创建虚拟儿科人群，将该模型扩展到JIA患者。最后，基于开发的阿达木单抗在JIA患者中的PBPK模型，对不同年龄组的给药方案进行了评估。结果：该研究成功开发并验证了阿达木单抗在成人和儿科人群中的PBPK模型。成人模型在0.5-2倍范围内的预测准确率为92.90%，儿童模型在0.5-2倍范围内的预测准确率为90.62%。对于小儿JIA患者，建议以年龄和体重为基础给药，以达到与成人相当的谷浓度。结论：建立了阿达木单抗在小儿JIA患者中的PBPK模型，为该人群的个性化给药方案提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.30

自引率

2.30%

发文量

127

期刊介绍： Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.