title: Pharmacokinetic study of salvianolic acid A in beagle dog after oral administration by a liquid chromatography-mass spectrometry method: a study on bioavailability and dose proportionality.
abstract: BACKGROUND
  Salvianolic acid A (SAA) is one of the main water-soluble components isolated from Salvia miltiorrhiza Bunge. Pharmacological researches revealed that it had various curative activities after oral and intravenous administration, including beneficial effects on diabetes and its complications, cardioprotective effect, anti-platelet aggregation, and so on. However, there is no report regarding the pharmacokinetics of SAA in beagle dogs after oral administration up to now.
  
  
  OBJECTIVE
  To study the pharmacokinetics of different doses of SAA in beagle dogs and figure out the absolute bioavailability and dose proportionality of SAA after oral administration.
  
  
  METHODS
  Male and female beagle dogs were orally administered SAA 5, 10 and 20mg/kg randomly. The plasma drug concentration was detected by a rapid, sensitive and reproducible liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic parameters were calculated from plasma concentration-time data using the DAS pharmacokinetic software Data Analysis System Version 3.0 program.
  
  
  RESULTS
  After single-dose oral administration of SAA, the mean peak plasma concentration (Cmax) values for groups treated with 5, 10 and 20 mg/kg doses ranged from 14.38 to 38.18 µg/L, and the mean area under the concentration-time curve (AUC(0-t)) values ranged from 38.77 to 130.33 (µg/L·h). SAA showed lack of dose proportionality over the dose range 5-20mg/kg, based on the power model. However, the increase in systemic exposure with dose appeared linear. The absolute bioavailability was calculated to range from 1.47% to 1.84%.
  
  
  CONCLUSIONS
  The pharmacokinetic properties of SAA in beagle dogs after oral administration were characterized as rapid oral absorption, quick clearance, and poor absolute bioavailability. Systemic exposure exhibited lack of dose proportionality over the dose range 5-20mg/kg. Furthermore, a readily preparative LC-MS method was demonstrated in this study for the research of traditional Chinese medicine.
authors.affiliation: Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Junke
authors.initials: J
authors.lastname: Song
authors.forename: Shuo
authors.initials: S
authors.lastname: Tian
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Zhangying
authors.initials: Z
authors.lastname: Feng
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002109:Caffeic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007773:Lactates / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008516:Medicine, Chinese Traditional / Q000379:methods; D011897:Random Allocation; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D002109:Caffeic Acids; D007773:Lactates; C066201:salvianolic acid A