4种药物联用在Beagle犬体内的药物动力学

Pharmacokinetics of Tramadol,Venlafaxine hydrochloride,Sulpiride and Rotundine after simultaneous administration in Beagles

目的测定舒必利、曲马多、颅通定和盐酸文拉法新联合给药后,Beagle犬体内的药物动力学的参数变化,揭示4种药物在Beagle犬体内的药物动力学特征。方法24只Beagle犬单次ig不同剂量的舒必利、曲马多、颅通定和盐酸文拉法新的均匀混合粉末,HPLC-Fluor法测定血浆中各成分的浓度,观察剂量增加对4种药物在体内的影响。结果曲马多高剂量组的t1/2较中、低剂量组延长,使Cmax和AUC0-∞显著增高;随着文拉法新剂量的增加,t1/2延长,Cmax和AUC0-∞显著增高;颅通定高剂量组与中、低剂量组比较,Cmax和AUC0-∞的差异均有统计学意义;舒必利亦呈相似的统计学结果。结论Beagle犬体内4种药物的药-时曲线变化均呈一室开放模型,梯度剂量给药后的药-时曲线显示剂量依赖关系,呈一级动力学过程;4种药物间存在药物的相互作用,影响各自在Beagle犬体内的药物动力学过程,尤其显著延长曲马多、万拉法新和舒必利的t1/2。

OBJECTIVE To determine the pharmacokinetic parameters of Tramadol, Venlafaxine hydrochloride, Sulpiride and Rotundine after simultaneous administration in Beagles to reveal the pharmacokinetic characteristics of these four components. METHODS 24 fasted Beagles were administrated the mixture at different doses orally, determined the concentration of the four components using HPLC - Fluor to look into the influence of dosage on in vivo progress of the components; sustained administration kept 7 d to detect the accumulation in vivo. New 8 Beagles were administrated each component respectively to measure the interaction each other. RESULTS t1/2 of Tramadol at high dose was longer than those at mid - and low - dose which increased Cmax and AUC0-∞ obviously, t1/2 of Venlafaxine prolonged, Cmax, AUC and AUC0-∞ increased with the dose increasing. Compared with mid - and low - dose, difference in Cmax and AUC0-∞ in high dose of Rotundine had significant difference as well as Sulphide. CONCLUSION The AUC change of Sulphide, Tmmadol, Rotundine and Venlafaxine follow one open - compartment model. The AUC after gradient- dosing administration reveals a dose - dependent relationship. The process in vivo takes on first order dynamic characteristics. Interaction exists among the four components working on the pharmaeokinetic progress of them, especially on the prolongation of t1/2 of Tramdol, Venlafaxine and Sulphide.