蝙蝠葛碱在犬体内的药代动力学和药效动力学研究

目的　应用药动学药效学结合模型方法研究蝙蝠葛碱在犬体内的药代动力学和药效动力学之间的关系。方法　4只beagle犬给蝙蝠葛碱6mg·kg-1静脉注射后,分时取血及行心电、血压及血流动力学变化观察。采用反相高效液相紫外法测定血浆中蝙蝠葛碱的浓度。结果　蝙蝠葛碱主要药动学参数T1 /2α,T1 /2β,Vd,AUC分别为(0 049±0 016)h,(2 .7±0. 6)h, (15. 8±3 5)L·kg-1和(1. 48±0. 17)mg·h·L-1。对Q Tc的最大延长率为( 25 5±9 4 )%;SBP,DBP,±(dp/dt)max的最大抑制率分别为( 23 .0±4. 9 )%,(21 .9±5. 9)%, ( 42. 8±6 .6 )%和( 39 .0±17 .1 )%。药理效应滞后于血药浓度10 ~15min。药理效应与效应室浓度之间的关系符合sigmoid Emax模型。结论　建立了蝙蝠葛碱在犬体内血药浓度、时间、药物效应三者之间的关系。

Pharmacokinetics and pharmacodynamics of dauricine in beagle dogs

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_(1/2α),T_(1/2β),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.