利奈唑胺在Beagle犬体内的药动学研究

目的建立测定Beagle犬血浆中利奈唑胺质量浓度的高效液相色谱法，研究其在Beagle犬体内的药物代谢动力学特征。方法5只Beagle犬灌胃给予利奈唑胺50mg／kg，于给药前及给药后0．083，0．17，0．33，0．66，1．0，1．5，2．0，4．0，6．0，8．0，12．0，24h采集血样，用高效液相色谱法测定血浆中利奈唑胺的质量浓度，血浆样品用10％三氯乙酸沉淀蛋白，流动相为甲醇-乙腈-水（20：20：60，V／V／V），检测波长25411In。采用DAS3．0程序计算药物代谢动力学参数。结果利奈唑胺质量浓度线性范围是0．20～40．0μg／mL（r=0．9993），平均绝对回收率为90．50％～95．20％，日内和日间RSD均小于12％。利奈唑胺在犬体内的主要药动学参数值，达峰浓度（Gmax）为（25．36±9．65）μg／mL，半衰期（t。，2）为（3．72±1．06）h，0～24h药时曲线下面积（AUCo-24）为（144．65±39．85）mg·h／L，0-∞药时曲线下面积（AUCo-∞）为（146．98±45．18）mg·h／L。结论该方法简便、快速，适用于体内利奈唑胺的测定及药动学研究。利奈唑胺在犬体内符合一室模型，消除较快，分布较广。

Study on in vivo Pharmacokinetics of Linezolid in Beagle dog

Objective To establish a HPLC method to detect the plasma concentration of linezolid in beagle dog and to study its pharmacokinetics in vivo. Methods 5 Beagle dogs were given linezolid 50 mg/kg by gavage. The blood sample was collected before drug administration and at 0,0. 083,0.17,0.33,0.66,1.0,1.5,2.0,4.0,6.0,8.0,12.0,24 h after drug administration. The plasma concentration of linezolid was determined by HPLC. The plasma sample was performed the protein precipitation by 10% trichloracetic acid. The mobile phase was methanol-acetonitrile-water（20：20：60, V/ V/ V）. The detection wavelength was 254 nm. The pharma- cokinetic parameters were calculated with DAS3.0 software. Results The linear range of linezohd was 0. 20- 40.0 p~g/mL（ r =0. 999 3）. The average recovery rate was 90.50%-95.20%. Both the within-day and between-day RSD were less than 12%.The main pharmacokinetic parameters were as follows ： Cmax （25.36 ±9.65 ） μg/mL, t1/2 （3.72 ± 1.06） h, A UC（o - 24） （ 144. 65 ± 39.85 ）mg h/L, AUC（0-∞）） （146.98 ± 45. 18）rag h/L. Conclusion This HPLC method is simple,rapid and suitable for the determination of in vivo linezolid and its pharmaeokinetic study. Linezolid fits to the one- compartment model in Beagle dog in vovo, its elimination is faster and distribution is wider.