[~3H]洛非西定在大鼠体内的药动学Pharmacokinetics of [~3H] lofexidine-HCl in rats
鲁澄宇,王海燕,许卫铭,谢湘林,吴铁
LU Cheng-Yu~1,WANG Hai-Yan~2,XU Wei-Ming~1,XIE Xiang-lin~3,WU Tie~1(1.Department of Pharmacology
摘要(Abstract)：
目的研究[3H]洛非西定在大鼠体内不同给药途径的药代动力学。方法TLC分离原型药物,液闪法测定血浆中药物放射性强度,用3P87程序计算药动学参数。结果大鼠iv[3H]洛非西定,其时-量曲线符合开放3室模型。t1/2pi为0.031~0.042 h,t1/2α为0.352~0.398 h,t1/2β为10.982~11.763 h。大鼠ig[3H]洛非西定,其时-量曲线符合开放2室模型。t1/2Ka为1.037~1.102 h,t1/2α为2.113~2.325 h,t1/2β为11.805~10.465 h,Tm ax为2.448~2.196 h,F为53%~55%。AUC和Cm ax与剂量呈线性关系。结论本方法适合洛非西定的药动学研究,测定结果为临床合理用药提供依据。
Objective To study the pharmacokinetics of -lofexidine in rats.Methods Parent drug concentration of lofexidine in plasma and tissues were determined by TLC method.The radioactivity of -lofexidine in plasma were determined with scintillation.The pharmacokinetic parameters of lofexidine in rats were calculated by 3P87 program.Results Concentration-time curves after iv administration at the dose of 0.05 or 0.2 mg/kg of -lofexidine in rats were fitted to the three-compartment model with t_(1/2pi) of 0.031~0.042 h,t_(1/2 α) of 0.352~0.398 h and t_(1/2β) of 10.982~11.763 h.Concentration-time curves after ig administration at the dose of 0.05 or 0.2 mg/kg of -lofexidine in rats were fitted to the two-compartment model with t_(1/2Ka) of 1.037~1.102 h,t_(1/2 α) of 2.113~2.325 h,t_(1/2β) of 11.805~10.465 h,T_(max) of 2.448~2.196h and the bioavailability(F) of 53%~55%.The area under curves(AUCs) and C_(max) were linearly over the dosages.Conclusion The method can be used in the pharmacokinetic study of lofexidine and provides evidence for clinical application.
关键词(KeyWords)：
洛非西定;大鼠;药代动力学;薄层色谱法
lofexidine;rats;pharmacokinetics;TLC
基金项目(Foundation):
作者(Author):
鲁澄宇,王海燕,许卫铭,谢湘林,吴铁
LU Cheng-Yu~1,WANG Hai-Yan~2,XU Wei-Ming~1,XIE Xiang-lin~3,WU Tie~1(1.Department of Pharmacology