Pharmacokinetics and pharmacodynamics of dauricine in beagle dogs / 中国药理学通报

ABSTRACT

Aim To investigate the relation between pharmacokinetics and pharmacodynamics of dauricine in dogs with the combined PK-PD model. Methods The plasma drug concentration was determined by a validated reversed-phase HPLC method that entailed ultraviolet detector and the effects on cardiac electrophsiology; blood pressure and hemodynamics were recorded by polygraph. Results The main pharmacokinetic parameters T_(1/2?),T_(1/2?),V_d, and AUC were (0.049?0.016) h, (2.7?0.6) h, (15.8?3.5) L?kg~(-1),and (1.48?0.17) mg?h?L~(-1),respectively.The maximal increase in Q-Tc intervals was(25.5?9.4)%, whereas the maximal decrease in SBP,DBP,?(dp/dt)_(max) were (23.0?4.9)%,(21.9?5.9)%,(42.8?6.6)%, and(39.0?17.1)%, respectively.The peak effects were detected approximately 10～15 min later than the plasma concentration. Relation between effects and effect compartments was analyzed with the sigmoid-E_(max) model. Conclusion The relation between plasma concentrations,time and effects is established in beagle dogs.