Purpose

Understanding local concentrations in intra-articular tissues and fluids such as cartilage, synovial membrane, and synovial fluid are a valuable tool to predict potential pharmacodynamic effects and efficacy of injection products and describe the effect of disease states on the disposition of drug.  Therefore, a PBPK model was developed that incorporates solubility, dissolution, particle size distribution, tissue or protein binding, diffusion, and uptake into systemic circulation of active pharmaceutical ingredients (APIs) in the knee joint capsule. Methotrexate (MTX) and triamcinoline acetonide (TCA) validation studies were conducted to test the new model and determine what future improvements are necessary.  This first step will accelerate the development of additional elbow joint models and facilitate disease state predictions.

By James Mullim, Maxime Le Merdy, Viera Lukacova, Michael B. Bolger

2019 AAPS Annual Meeting PharmSci 360, November 3-6, 2019, San Antonio, Texas