Molecules, Vol. 23, Pages 987: A Microdialysis in Adjuvant Arthritic Rats for Pharmacokinetics –Pharmacodynamics Modeling Study of Geniposide with Determination of Drug Concentration and Efficacy Levels in Dialysate

In this study, an articular cavity microdialysis sampling system for adjuvant arthritic (AA) rats was established to study the effect of GE on the release of prostaglandin E2 (PGE2) in AA rats induced by Freund’s complete adjuvant (FCA). An UHPLC-MS/MS method was developed to determine the concentrations of GE and PGE2 in the dialysate. Through the determination of drug concentrations and PGE2 efficacy levels in the dialysate, the developed methods were successfully applied to set up concentration–time and effect–time profiles followed by PK–PD modeling of GE’s effect on decreasing PGE2 release after oral administration of GE. The effect was well described by the developed PK–PD modeling, indicating that GE may play an anti-inflammatory role via decreasing AA-induced elevated PGE2 levels. In the selection of suitable endogenous small molecules as effect markers, the establishment of AA rat joint-cavity microdialysis is an attractive technique for rational PK–PD studies.
Source: Molecules - Category: Chemistry Authors: Tags: Essay Source Type: research