美索巴莫磷酸钠在大鼠体内的药代动力学研究

Pharmacokinetic features of methocarbamal sodium phosphate in rats

目的:研究灌胃和肌内注射给予美索巴莫磷酸钠后在大鼠体内的药代动力学特征。方法:应用高效液相色谱法测定大鼠血浆中的美索巴莫浓度,以3P97药代动力学软件拟合药代动力学参数。结果:美索巴莫磷酸钠以128、256和512 mg/kg单次灌胃给药后,主要药代动力学参数t1/2分别为(0.86±0.28)、(1.50±0.47)和(2.74±1.31)h;C_(max)分别为(39.09±11.60)、(58.97±20.22)和(82.62±21.44)μg/ml;AUC_(0-t)分别为(75.00±28.58)、(175.94±94.77)和(350.05±122.99)μg/ml·h。美索巴莫磷酸钠以128、256和512 mg/kg单次肌内注射给药后,主要药代动力学参数t1/2分别为(1.15±0.45)、(1.44±0.59)和(1.95±0.82)h;C_(max)分别为(75.98±18.83)、(117.00±16.51)和(157.85±13.26)μg/ml;AUC_(0-t)分别为(145.36±53.64)、(270.57±109.38)和(467.52±210.05)μg/ml·h。结论:美索巴莫磷酸钠灌胃或肌注给药后在大鼠体内的药代动力学过程符合一级吸收一房室开放模型特点,随剂量的增加,消除半衰期t1/2、峰浓度C_(max)和曲线下面积AUC_(0-t)均有相应的增高趋势。

Objective:To investigate the pharmacokinetic characteristics of methocarbamol sodium phosphate(Me-Na)in rats after intragastric and intramuscular administration.Methods:The rat plasma concentrations of methocarbamol were determined by HPLC.Pharmacokinetic parameters were evaluated by 3P97 software.Results:For intragastric administration of Me-Na at a single doses of 128,256 or 512 mg/kg,the main pharmacokinetic parameters were as follows:t 1/2 was(0.86±0.28),(1.50±0.47)and(2.74±1.31)h,respectively;C max was(39.09±11.60),(58.97±20.22)and(82.62±21.44)μg/ml,respectively;AUC(0-t)was(75.00±28.58),(175.94±94.77)and(350.05±122.99)μg/ml·h,respectively.While Me-Na was intramuscularly injected at a single dose of 128 mg/kg,256 mg/kg,or 512 mg/kg,respectivels,the main pharmacokinetic parameters were as follows:t 1/2 was(1.15±0.45),(1.44±0.59)and(1.95±0.82)h,respectively;C max was(75.98±18.83),(117.00±16.51)and(157.85±13.26)μg/ml,respectively;AUC(0-t)was(145.36±53.64),(270.57±109.38)and(467.52±210.05)(μg/ml)·h,respectively.Conclusions:The characteristics of pharmacokinetic processes of Me-Na in rats after intragastric administration and intramuscular injection are in consistence with one compartment open model.With the increase of the dose,the elimination half-lives t 1/2,the peak concentrations C max and the areas under the curve AUC(0-t)exhibit a tendency to increase correspondingly.