Pharmacokinetic-pharmacodynamic modeling of Laportea bulbifera extract in adjuvant-induced arthritis rats via joint cavity microdialysis

This study developed a local pharmacokinetic-pharmacodynamic (PK-PD) model for Laportea bulbifera extract (LBE) in the joint cavity of adjuvant-induced arthritis (AA) rats using microdialysis technology. A stable intra-articular microdialysis sampling system was established, and the PK behavior of LBE in the joint cavities of normal and AA rats was compared using ultra performance liquid chromatography-tandem mass spectrometry analysis. The results demonstrated that the time to peak concentration and absorption half-life of the components were shortened in AA rats, whereas the area under the concentration-time curve increased. An increase in the apparent volume of distribution and a decrease in clearance were also observed, indicating accelerated absorption, increased exposure, and prolonged retention. An integrated PK-PD model was constructed by combining these data with pharmacodynamic data for tumor necrosis factor-alpha, interleukin-6, interleukin-1β, and rheumatoid factor (RF) obtained by enzyme-linked immunosorbent assay. Based on half maximal inhibitory concentration, the inhibitory potency of the five components against the four biomarkers was ranked as follows: kaempferol-3-O-rutinoside > neochlorogenic acid > rutin > chlorogenic acid > cryptochlorogenic acid. The effect compartment model revealed a linear relationship between RF and multiple components, underscoring RF's potential role as a key therapeutic target in the joint cavity. This study represents the first systematic elucidation of the local PK-PD characteristics of LBE, providing a scientific basis for developing this Miao medicinal herb and its clinical application in rheumatoid arthritis.