title: Pharmacokinetic-pharmacodynamic modeling of daurisoline and dauricine in beagle dogs.
abstract: OBJECTIVE
  To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of daurisoline and dauricine, and compare their effects on cardiac electrophsiology, blood pressure, and hemodynamics in beagle dogs.
  
  
  METHODS
  The plasma drug concentration was determined by the reversed-phase HPLC method and the effects on cardiac and hemodynamics were recorded by polygraph. The pharmacokinetic and PK-PD model parameters were calculated.
  
  
  RESULTS
  The pharmacokinetics were best fitted to a two-compartment open model, and the relationship between effect and effect compartment concentration of both drugs could be represented by the sigmoid-E(max) model. There were no significant differences in main pharmacokinetics and PK-PD parameters between the two drugs.
  
  
  CONCLUSIONS
  No statistically different kinetic disposition characteristics and potencies of inhibitory effects on myocardial function of daurisoline and dauricine were found in beagle dogs.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. sjshi1@163.com.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Shi
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Shi-Fen
authors.initials: SF
authors.lastname: Gu
authors.forename: Fan-Dian
authors.initials: FD
authors.lastname: Zeng
mesh_terms: D000470:Alkaloids; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D031603:Menispermum / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D044005:Tetrahydroisoquinolines / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D044182:Benzylisoquinolines; D044005:Tetrahydroisoquinolines; C023968:daurisoline; C035934:dauricine