摘要
目的研究大鼠体内格列齐特对华法林钠药效学和药动学的影响。方法采用HPLC法测定大鼠体内华法林钠的血药浓度,比较华法林钠单独给药,与格列齐特合并用药后的药物动力学参数,根据AUC0～t与ρmax,进行t检验;测定单独用药组、合并用药组的主要药效学参数凝血酶原时间tPT(prothrombin time,PT)和国际标准化比值(international normalizde ratio,INR),进行方差分析。结果药动学参数显示,合并用药组与单独用药组相比,tmax、t1/2显著延长,Ke值显著降低,ρmax、AUC0～t和AUC0-∞显著减少(P【0.05);格列齐特显著改变了大鼠体内华法林钠主要药效学参数tPT和INR(P【0.05)。结论格列齐特对大鼠体内华法林钠的药效学和药动学参数有显著影响,因此在联合用药时应适当调整剂量,或者及时监测凝血时间以预测血栓或出血发生的可能性,防止不良反应的发生。
Objective To study the effect of gliclazide on the pharmacodynamics and pharmacokinetics of warfarin sodium in rats.Methods The plasma concentration of warfarin sodium was measured using a validated HPLC method with a ultraviolet detector.The plasma concentration-time data were accessed by DAS2.0 and the pharmacokinetic parameters were obtained.Influence of gliclazide on the pharmacodynamics and pharmacokinetics of warfarin sodium was evaluated by t-test.Results Compared to the warfarin sodium alone group, tmax, t1/2 increased, Ke , Cmax , AUC0～t and AUC0-∞ decreased significantly in the warfarin sodium combining gliclazide group.Gliclazide had significant influence on the pharmacokinetic and pharmacodynamics parameters of warfarin sodium.Conclusions The study showed that gliclazide has obvious effect on the pharmacokinetic and pharmacodynamics parameters of warfarin sodium in vivo.It is suggested that the dose should be adjusted appropriately when warfarin sodium and gliclazide are used together in clinic to prevent potential adverse effects.Also, the clotting time should be monitored to reduce the risk of thrombosis or hemorrhage.
出处
《中国药剂学杂志（网络版）》
2010年第4期110-116,共7页
Chinese Journal of Pharmaceutics：Online Edition
关键词
药剂学
药物相互作用
药效学
药动学
华法林钠
格列齐特
pharmaceutics
interaction
pharmacodynamics
pharmacokinetics
warfarin sodium
gliclazide
