title: Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison.
abstract: There is evidence suggesting that herbal extracts demonstrate greater bioactivities than their isolated constituents at an equivalent dose. This phenomenon could be attributed to the absence of interacting substances present in the extracts. By measuring the pharmacokinetic parameters of paeoniflorin (PF) and albiflorin (AF) after being orally administered to rats in isolated form, in combination with each other and within total peony glucosides (TPG), respectively, the current study aimed to identify positive pharmacokinetic interactions between components of peony radix extracts. Moreover, the pharmacokinetic profiles of PF and AF under normoxia and hypoxia were also investigated and compared. In order to achieve these goals, a highly sensitive and reproducible ultra-peformance liquid chromatography-mass spectrometry (UPLC-MS) method was developed and validated for simultaneously quantitation of PF and AF in rat plasma. This study found that compared with that of single component (PF/AF), the exposure of PF in rat plasma after combination administration or TPG administration was significantly increased, meanwhile the elimination of PF/AF was remarkably reduced. It was also noticed that AUC and Cmax of PF in hypoxia rats were significantly decreased compared with that of normaxia rats, suggesting that there was a decreased exposure of PF in rats under hypoxia. The current study, for the first time, revealed the pharmacokinetic interactions between PF/AF and other constitutes in TGP and the pharmacokinetic profiles of PF and AF under hypoxia. In view of the current findings, it could be supposed that the clinical performance of total peony glucosides would be better than that of single constitute (PF/AF). The outcomes of this animal study are expected to serve as a basis for development of clinical guidelines on total peony glucosides usage.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. xwzccmu@126.com.
authors.forename: Weizhe
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. 13520339253@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. jin_mo@live.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. gbb624@163.com.
authors.forename: Beikang
authors.initials: B
authors.lastname: Ge
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. gongww12345@126.com.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Gong
authors.affiliation: Core Facilities Center, Capital Medical University, Beijing 100069, China. wuyt@163.com.
authors.forename: Yingting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. madingdaier@aliyun.com.|Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing 100069, China. madingdaier@aliyun.com.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. yumingzhao@ccmu.edu.cn.|Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing 100069, China. yumingzhao@ccmu.edu.cn.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. syxpx88@163.com.|Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing 100069, China. syxpx88@163.com.
authors.forename: Pingxiang
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. xuem@ccmu.edu.cn.|Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing 100069, China. xuem@ccmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics; D005960:Glucosides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D000860:Hypoxia; D008297:Male; D015394:Molecular Structure; D039821:Monoterpenes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D029596:Paeonia / Q000737:chemistry*; D051381:Rats; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D006027:Glycosides
chemical_list: D001952:Bridged-Ring Compounds; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides; C014959:albiflorin
keywords: UPLC-MS/MS; albiflorin; hypoxic; interaction; paeoniflorin; pharmacokinetics; total peony glucosides