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Molecules. 2018 Apr 24;23(5). pii: E987. doi: 10.3390/molecules23050987.

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

Author information

1
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. wuhongprof@aliyun.com.
2
Bozhou Chuangxin Technology Consulting Co. Ltd., Bozhou 236800, China. 18605538039@163.com.
3
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. wuhuancpu@ahtcm.edu.cn.
4
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. yunjing_82@126.com.
5
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. 18605538039@163.com.
6
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. daili6daisy@163.com.
7
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. zhangzhengrong311@126.com.
8
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. fujun6866@163.com.
9
College of Pharmacy, Anhui University of Chinese Medicine, Key Laboratory of Modernized Chinese Medicine in Anhui Province, Hefei 230012, China. fengli92@aliyun.com.

Abstract

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.

KEYWORDS:

PK–PD modeling; UHPLC-MS/MS; geniposide; microdialysis; prostaglandin E2; rheumatoid arthritis

PMID:
29695042
PMCID:
PMC6099731
DOI:
10.3390/molecules23050987
[Indexed for MEDLINE]
Free PMC Article

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