College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China.
Bozhou Chuangxin Technology Consulting Co. Ltd., Bozhou 236800, China.
Molecules. 2018 Apr 24;23(5):987. doi: 10.3390/molecules23050987.
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 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 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.
微透析是一种在临床前和临床研究中用于药代动力学-药效学（PK-PD）建模的采样方法，是一种方便的体内采样技术。京尼平苷（GE）是环烯醚萜糖苷类化合物，是栀子果实的主要活性成分，具有抗炎作用。本研究建立了关节腔微透析采样系统，用于研究京尼平苷对弗氏完全佐剂（FCA）诱导的佐剂性关节炎（AA）大鼠前列腺素 E₂（PGE₂）释放的影响。建立了 UHPLC-MS/MS 方法来测定透析液中京尼平苷和 PGE₂的浓度。通过测定透析液中药物浓度和 PGE₂药效水平，成功应用所建立的方法建立了 GE 对口服给药后降低 PGE₂释放的作用的浓度-时间和效应-时间曲线，并进行 PK-PD 建模。该作用通过所建立的 PK-PD 模型得到了很好的描述，表明 GE 可能通过降低 AA 诱导的升高的 PGE₂水平发挥抗炎作用。在选择合适的内源性小分子作为效应标志物时，建立 AA 大鼠关节腔微透析是进行合理 PK-PD 研究的一种有吸引力的技术。
