title: Integrated pharmacokinetics and biodistribution of multiple flavonoid C-glycosides components in rat after oral administration of Abrus mollis extract and correlations with bio-effects.
abstract: BACKGROUND
  Abrus mollis, a commonly used traditional Chinese medicine in China and other Asia countries, has been used clinically to prevent and treat hepatitis and alcoholic liver disease for decades.
  
  
  METHODS
  A modified HPLC-MS method was developed for the determination of vicenin-2 (AM-I), isoschaftoside (AM-II), and schaftoside (AM-III) of AM extract (AME) in rat plasma and tissues (heart, liver, spleen, lungs, and kidneys). Following oral administration of AME to rat at a dose of 200mg/kg, the concentrations of AM-I, II and III in plasma and tissues were quantified. An integrated double peak pharmacokinetics model was used to fit the concentration-time curves. The effects of drug on the bile flow and toe swelling of rats induced by carrageenan were also studied.
  
  
  RESULTS
  The limit of quantitation of this modified HPLC-MS method decreased from 25 to 5ng/mL for plasma and from 100 to 10ng/g for tissue. These concentration-time curves show two successive maximum concentrations. The results of integrated double peak pharmacokinetics in this paper indicated that the three flavonoid C-glycosides may be absorbed by two sites of intestine in vivo. These results of bile flow and toe swelling showed a significant correlation between the pharmacokinetics and pharmacodynamics.
  
  
  CONCLUSIONS
  The novel integrated double peak pharmacokinetic approach to studying the holistic pharmacokinetic properties of traditional Chinese medicine has been successfully developed and validated using AM as a model drug. This study would be a useful guide for the holistic double peak pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wanghao@cpu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Drug Screening Laboratory, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Huo
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D029912:Abrus; D000284:Administration, Oral; D000818:Animals; D047310:Apigenin / Q000097:blood / Q000378:metabolism*; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005960:Glucosides / Q000097:blood / Q000378:metabolism*; D006027:Glycosides / Q000097:blood / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D009206:Myocardium / Q000378:metabolism; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D005960:Glucosides; D006027:Glycosides; D010936:Plant Extracts; C530449:apigenin-6,8-di-C-glycopyranoside; C515112:schaftoside; D047310:Apigenin; D002351:Carrageenan; C515113:isoschaftoside
keywords: Abrus mollis; Correlation between pharmacokinetics and bio-effect; Double peak curve; Flavonoid C-glycosides; Integrated pharmacokinetics