A Microdialysis in Adjuvant Arthritic Rats for Pharmacokinetics⁻Pharmacodynamics Modeling Study of Geniposide with Determination of Drug Concentration and Efficacy Levels in Dialysate.
A Microdialysis in Adjuvant Arthritic Rats for Pharmacokinetics⁻Pharmacodynamics Modeling Study of Geniposide with Determination of Drug Concentration and Efficacy Levels in Dialysate.
复制标题
佐剂关节炎大鼠微透析用于京尼平苷药代动力学-药效学模型研究并测定透析液中的药物浓度和功效水平
DOI：
10.3390/molecules23050987
复制
发表时间：
2018-04-24
期刊：
影响因子：
--
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Deng R;Wang W;Wu H;Zhang Y;Wang W;Dai L;Zhang Z;Fu J;Li F
微透析是一种方便的体内取样技术，可用于临床前和临床研究的药代动力学-药效学（PK-PD）建模。栀子苷（Geniposide，GE）是栀子果实的主要活性成分，具有抗炎作用，是一种环烯醚萜苷类化合物。本研究建立佐剂性关节炎（AA）大鼠关节腔微透析取样系统，研究GE对弗氏完全佐剂（FCA）诱导的AA大鼠前列腺素E2（PGE 2）释放的影响。开发了一种UHPLC-MS/MS方法来测定透析液中GE和PGE 2的浓度。通过测定透析液中的药物浓度和PGE 2疗效水平，成功地应用所开发的方法建立了浓度-时间和效应-时间曲线，然后对口服GE后GE降低PGE 2释放的作用进行PK-PD建模。该作用通过所开发的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PGE 2水平而发挥抗炎作用。在选择合适的内源性小分子作为效应标志物方面，AA大鼠关节腔微透析技术的建立是一种合理的PK-PD研究的有吸引力的技术。
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 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.
登录
查看更多内容
影响因子：
5
作者：
Moudgil, Kamal D.;Kim, Peter;Brahn, Ernest
通讯作者：
Brahn, Ernest
影响因子：
6.7
作者：
Milligan, P. A.;Brown, M. J.;Lalonde, R. L.
通讯作者：
Lalonde, R. L.
基于生物信息学的 MicroRNA 调节和类风湿关节炎相关基因的鉴定
影响因子：
3.7
作者：
Song YJ;Li G;He JH;Guo Y;Yang L
通讯作者：
Yang L
影响因子：
4.6
作者：
Kim KW;Kim BM;Lee KA;Lee SH;Firestein GS;Kim HR
通讯作者：
Kim HR
影响因子：
4.9
作者：
Lowin T;Apitz M;Anders S;Straub RH
通讯作者：
Straub RH