盐酸戊乙奎醚在小鼠体内的药动学研究

Study on pharmacokinetics of penehyclidine hydrochloride in mice

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 .0 5 ,0 .15和 0 .4 5mg·kg-13种剂量后的主要动力学参数tmax为 0 .13,0 .10和 0 .0 9h ;t1/2 β为 2 .35 ,2 .36 ,2 .6 0h ;cmax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 .15mg·kg-1后 ,很快分布到全身各组织中 ,给药后 2 0min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 2 4h由尿和粪约排出 4 % ;小鼠肌注同剂量的3 H 盐酸戊乙奎醚后 ,2 4h由尿和粪中累积排出6 1.11%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 6 0 .0 9%和 4 1.79%。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。

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. 45 mg&middotkg-1. tmax and t1/2β were found to be 0.09∼0.13 h and 2.35∼2.60h, respectively. cmax and AUC were increased linearlly to the administered dose with correlation coefficient of 0.999 and 0.994. After single im injection of 0.15mg&middotkg-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.