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

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