盐酸戊乙奎醚在小鼠体内的药动学研究

 目的研究盐酸戊乙奎醚在小鼠体内的药动学特性。方法小鼠肌注盐酸戊乙奎醚进行体内药动学实验，采用放射受体和放射性同位素方法测定生物样品中的药物浓度。结果小鼠肌注盐酸戊乙奎醚0.05，0.15和0.45 mg·kg^-13种剂量后的主要动力学参数t_max为0.13，0.10和0.09 h；t_1/2β-为2.35，2.36，2.60 h；c_max和AUC与给药剂量呈线性倍增。小鼠单剂量肌注盐酸戊乙奎醚0.15 mg·kg^-1后，很快分布到全身各组织中，给药后20 min各组织中的药物浓度均达到峰值；药物原形和具有药理活性的代谢产物24 h由尿和粪约排出4%；小鼠肌注同剂量的3H盐酸戊乙奎醚后，24 h由尿和粪中累积排出61.11%和7.31%。盐酸戊乙奎醚与小鼠和人血浆蛋白的结合率分别为60.09% 和41.79%。结论小鼠肌注盐酸戊乙奎醚后吸收和分布均很快，药物主要以无药理活性的代谢产物形式由尿排出体外，与血浆蛋白的结合率中等。

Study on pharmacokinetics of penehyclidine hydrochloride in mice

OBJECTIVE To study the pharmacokinetics of penehyclidine hydrochloride (PCHE) in mice. METHODS The drug concentration in biological samples was determined by RRA and［3H］PCHE trace method. RESULTS The concentration time curves of PCHE in blood followed an open two compartment model with first order absorption after im administration of 0.05,0.15 and 0.45mg·kg^-1.t_maxand t_1/2β-were found to be 0.09～0.13 h and 2.35～2.60h,respectively.c_maxand AUC were increased linearlly to the administered dose with correlation coefficient of 0.999 and 0.994.After single im injection of 0.15mg·kg^-1,PCHE was distributed rapidly to various tissues.After 20 min,the drug levels in tissues reached the maximum concentrations with the highest in mandibular gland.About 61.11% and 7.31% of the total dosage were excreted from urine and feces within 24 h,respectively.The binding of PCHE to human and mice plasma protein were 41.79% and 60.09%,respectively. CONCLUSION After im administration to mice,PCHE is well absorbed,rapidly distributed and excreted via urine mainly as inactive metabolites.The protein binding was found to be medium.