Project Details

Pharmacokinetic Modeling to Optimize Dosing in Pediatric Rheumatic Diseases

Stephen Balevic, MD, PhD, MHS

Summary

BACKGROUND: Pediatric lupus (pSLE), juvenile dermatomyositis (JDM), and autoimmune uveitis (AU) affect approximately 50 in 100,000 children worldwide, virtually all of whom receive treatment with at least one off-label drug. However, these off-label drugs lack the pharmacokinetic (PK) data necessary to determine safe and effective dosages. GAP: Due to a lack of PK data, children with pSLE, JDM, and AU routinely receive inappropriate medication doses that do not account for their unique disease, resulting in treatment failure or toxicity. Physiologic based pharmacokinetic (PBPK) modeling is an innovative tool that can be used to optimize dosing in children who have altered physiology from their rheumatic disease. In this proposal, we will develop PBPK models and determine the optimal dosing for the three most common off-label drugs in children with pSLE, JDM, and AU. HYPOTHESIS: PBPK models will successfully characterize drug PK across a variety of rare pediatric rheumatic diseases and provide a dose individualization approach for children. METHODS: This is a pharmacokinetic study which will use existing, published data to develop and validate PBPK models for three off-label drugs of interest (IVIG, cyclophosphamide, and adalimumab), and then use the models to conduct dosing simulations in virtual populations of children with pSLE, JDM, and AU. RESULTS: Pending. IMPACT: This study will improve the clinical care of children by optimizing the dosing for the most common drugs used in patients with pSLE, JDM, and AU, thereby reducing disease activity and improving outcomes.