兔体内甲硝唑磷酸酯与甲硝唑的药代动力学研究

 为了研究水溶性甲硝唑前体制剂的药物动力学特性，本文建立了能同时测定血浆中甲硝唑和药物前体甲硝唑磷酸酯的高效液相色谱法。用此法测定了6只兔静脉交叉给予甲硝唑和甲硝唑磷酸酯后不同时刻的血药浓度，用非线性最小二乘法进行了药时曲线模型拟合。甲硝唑磷酸酯体内水解过程符合一级动力学，其水解速率常数为0．156／min。交叉给予这2种药物后，体内甲硝唑的药时过程均符合线性二室开放模型，药动学参数比较，两者无显著性差异。实验表明甲硝唑磷酸酯在兔体内能迅速水解，并不改变甲硝唑原有药动学特性。

Pharmacokinetics of metronidazole-phosphate and metronidazole in rab-bits

Metronidazole-phosphate preparation is a new parenteral dosage pharmacokineticsform. To study pharmacokinetics of metronidazole-phosphate(MNP)preparation,we establishedHPLC method for measuring the level of MNP,metronidazole(MTZ)and their metabolites inplasma simuItaneously. This method was simple,sensitive,reproducible and had a better linearity. Drug level in plasma of 6 rabbits after iv administration of MNP and MTZ by cross-over designwas determined,Drug level time course of MNP was a first-order elimenation process with a elim-ination constant 0.165min￣(-1)(n=6).The C vs t data of MTZ were fitted to two-compartmentmodel by nonlinear leastsquares method(Damping Gauss-Newton).The pharmacokinetic param-eters of MTZ and MNP after iv administraation showed no significant differences(P>0. 05,n=6).The results show that MNP was hydrolyzed into MTZ in rabbits rapidly.