A Microdialysis in Adjuvant Arthritic Rats for Pharmacokinetics–Pharmacodynamics Modeling Study of Geniposide with Determination of Drug Concentration and Efficacy Levels in Dialysate

Microdialysis, a sampling method for pharmacokinetics–pharmacodynamics (PK–PD) modeling in preclinical and clinical studies, is a convenient in vivo sampling technique. Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis fruit which has an anti-inflammatory effect. 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 E(2) (PGE(2)) in AA rats induced by Freund’s complete adjuvant (FCA). An UHPLC-MS/MS method was developed to determine the concentrations of GE and PGE(2) in the dialysate. Through the determination of drug concentrations and PGE(2) 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 PGE(2) 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 PGE(2) 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.