Pharmacokinetic-pharmacodynamic modeling of daurisoline and dauricine in beagle dogs.
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.
Shi
Shao-Jun
SJ
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. sjshi1@163.com.
Chen
Hui
H
Gu
Shi-Fen
SF
Zeng
Fan-Dian
FD
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
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D044182:Benzylisoquinolines; D044005:Tetrahydroisoquinolines; C023968:daurisoline; C035934:dauricine