title: Pharmacokinetics and tissue distribution of five bufadienolides from the Shexiang Baoxin Pill following oral administration to mice.
abstract: BACKGROUND
  Shexiang Baoxin Pill (SBP) is a well-known composite formula of traditional Chinese medicine (TCM), widely used to treat cardiovascular diseases such as angina pectoris and myocardial infarction. Bufadienolides are major active compounds of Venenum Bufonis, which is one of the seven materiamedicas that comprise the Shexiang Baoxin Pill. Previous pharmacokinetics studies of bufadienolides have typically used a single medicinal material delivered to rats. In this study, we have chosen the mouse, a more proper animal model than the rat, to investigate the in vivo pharmacokinetics and tissue distribution of bufadienolides from the Shexiang Baoxin Pill.
  
  
  METHODS
  The concentrations of bufadienolides in plasma and tissues were identified using high performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS). The samples were prepared by liquid-liquid extraction with ethyl acetate, and the separation of bufadienolides was achieved using an ACQUITY HSS T3 column by gradient elution using water (containing 0.1% formic acid) and acetonitrile as the mobile phase at a flow rate of 0.3 mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis.
  
  
  RESULTS
  The results showed that the five bufadienolides were rapidly absorbed and distributed into the body. The pharmacokinetic curve showed double peaks after oral administration. The major tissue depots for resibufogenin, bufalin, and bufotalin in mice were the intestines, lung and kidney, whereas the major tissue depots of gamabufotalin and arenobufagin were the intestines, liver and kidney.
  
  
  CONCLUSIONS
  The information gained from this research provides a meaningful insight for the clinical applications of the Shexiang Baoxin Pill.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, China.
authors.forename: Huimei
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Clinical Pharmacology, Beijing Military Command General Hospital, Beijing 100700, China.
authors.forename: Yongge
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lv
authors.affiliation: School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, China.
authors.forename: Wanlin
authors.initials: W
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Ge
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, China; Department of Clinical Pharmacology, Beijing Military Command General Hospital, Beijing 100700, China. Electronic address: wdzhangy@hotmail.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, China. Electronic address: lyliurh@126.com.
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002018:Bufanolides / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D013607:Tablets; D014018:Tissue Distribution
chemical_list: D002018:Bufanolides; D004365:Drugs, Chinese Herbal; D013607:Tablets; C526712:shexiang baoxin
keywords: Bufadienolides; LC–ESI-MS/MS; Pharmacokinetic; Resibufogenin (PubChem CID: 10063); Shexiang Baoxin Pill; Tissue distribution; arenobufagin (PubChem CID: 10051); bufalin (PubChem CID: 9547215); bufotalin (PubChem CID: 12302120); gamabufotalin (PubChem CID: 259803); tinidazole (PubChem CID: 5479)