Development of PBPK model for intra-articular injection in human: methotrexate solution and rheumatoid arthritis case study.

ABSTRACT: A physiologically based model describing the dissolution, diffusion, and transfer of drug from the intra-articular (IA) space to the plasma, was developed for GastroPlus® v9.8. The model is subdivided into compartments representing the synovial fluid, synovium, and cartilage. The synovium is broken up into two sublayers. The intimal layer acts as a diffusion barrier between the synovial fluid and the subintimal layer. The subintimal layer of the synovium has fenestrated capillaries that allow the free drug to be transported into systemic circulation. The articular cartilage is broken up into 10 diffusion sublayers as it is much thicker than the synovium. The cartilage acts as a depot tissue for the drug to diffuse into from synovial fluid. At later times, the drug will diffuse from the car

SUBMITTER: Le Merdy M 

PROVIDER: S-EPMC8604827 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature