头孢硫脒在小鼠的药动学研究

The pharmacokinetics study of cefathiamidine in mice

目的 研究头孢硫脒在小鼠中的药动学.方法 取24只小鼠,随机分为4组,每组6只,分别静脉给予7.3、29.2、116.8和467.6mg/kg的头孢硫脒,采集不同时间点的血样,分离血浆,使用经过确证的LC-MS/MS方法测定血浆中头孢硫脒的浓度,用WinNonlin软件中的非房室模型计算药动学参数.结果 静脉给药后,获得的主要药动学参数如下：T1/2分别为（0.20±0.03）、（0.33±0.05）、（0.27±0.08）和（0.38±0.10）h;AUC0～∞分别为（2.85±0.63）、（11.31±1.71）、（53.38±17.57）和（374.9±134.7）h·mg/L;Cax值分别为（9.53±2.10）、（46.67±9.50）、（170.18±71.02）和（1004.0±166.2）mg/L.结论 本文建立了快速、灵敏测定小鼠血浆中头孢硫脒的LC-MS/MS方法,并用于头孢硫脒在小鼠中的药动学研究.药动学结果显示,该药体内消除很快,不同剂量间的药动学参数呈现比较明显的相关关系.

Objective To investigate the pharmacokinetics of cefathiamidine in mice. Methods 24 mice were randomly divided into four groups （n=6）, blood samples were collected at different time intervals following intravenous injection of cefathiamidine at one of the four doses （7.3, 29.2, 116.8 and 467.6mg/kg）. The cefathiamidine concentrations in mice plasma were determined by a validated LC-MS/MS method and the pharmacokinetic parameters were calculated by using WinNonlin software program with non-compartmental model. Results The main pharmacokinetic parameters after intravenous injection of cefathiamidine were as follows： T1/2 were （0.20±0.03）, （0.33±0.05）, （0.27±0.08） and （0.38±0.10）h respectively. AUC0～∞ were （2.85±0.63） , （11.31±1.71） , （53.38±17.57） and （374.9±134.7）h.mg/L, respectively. Cax were （9.53±2.10）, （46.67±9.50）, 070.18±71.02） and （1004.0±166.2） mg/L respectively. Conclusion The established LC-MS/MS method for the determination of cefathiamidine in mice plasma was rapid and sensitive, and was applied to the pharmacokinetic study of cefathiamidine in mice. The pharmacokinetic results showed that the drug was eliminated fast and the pharmacokinetic parameters among different doses correlated well with each other.