Methotrexate pharmacokinetics after intraarticular injection in patients with rheumatoid arthritis

Disappearance kinetics of solutes from synovial fluid after intra‐ articular injection.

“…If an average synovial fluid volume (accessible by aspiration) of 33 ml is assumed [18], the approximate clearance of these solutes is 0.02 to 0.2 1 h-1. The clearance of methotrexate after intra-articular injection is 0.017 1 h-1 [19].…”

Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint

“…1,2 However, the therapeutic outcome following IA injection is considerably lessened by drug delivery issues that include rapid clearance into the systemic circulation from the synovial ultrastructure, which offers little barrier to the diffusion of molecules in and out of a joint. 4,5 Knight and Levick 6 found that the synovial surface consists of a discontinuous layer of synoviocytes (covering 80% of the synovial lining) with wide intercellular gaps measuring 0.1-5.5 μm with no basal membrane. The IA route is even comparable to intramuscular or subcutaneous routes pharmacokinetically with regard to rapid redistribution of drug into the bloodstream.…”

Intra-articular methotrexate associated to lipid nanoemulsions: anti-inflammatory effect upon antigen-induced arthritis

“…5 To circumvent the systemic toxicity of MTX, the use of the intra-articular route of drug administration was tested, but the results were not satisfactory because MTX is rapidly cleared from the joint cavity. 6 In previous studies, we showed that nanoemulsions (LDE) that resemble the lipid structure of low-density lipoprotein (LDL) have the ability to concentrate in tissues undergoing proliferating processes, such as in malignant neoplasias or atherosclerotic lesions. 7,8 LDE binds to LDL receptors, which are upregulated in those tissues, and this is the mechanism that favors the uptake and intracellular concentration of LDE via the receptor-mediated endocytosis pathway.…”