单次静脉注射后多西环素在大鼠血浆和尿液中的药物动力学研究  

Pharmacokinetics Studies of Doxycycline in Rats′Plasma and Urine after Single Intravenous Administration

作　　者：杨帆[1] 赵振升[1] 孟小宾 孔涛[1] 王国永[1] 周变华[1] 郝雪琴[1] 

机构地区：[1]河南科技大学动物科技学院,河南洛阳471003 [2]天津瑞普生物技术股份有限公司,天津300300

出　　处：《动物医学进展》2015年第7期52-56,共5页Progress In Veterinary Medicine

基　　金：河南科技大学博士启动基金项目(09001677)

摘　　要：选用7只平均体重为250g±31g的健康雄性成年大鼠,进行多西环素单剂量静脉注射(10mg/kg体重)给药途径下的血浆和尿液药物动力学研究。采用高效液相色谱法检测血浆及尿液中的药物浓度,之后分别采用房室分析和速度法计算血浆和尿液中多西环素的药物动力学参数。健康大鼠静脉注射多西环素后,血浆浓度-时间数据的最优拟合模型为二室开放模型。主要药物动力学参数如下:表观分布容积(Vd)为(1 493.48±243.65)mL/kg、分布速率常数(α)为(13.70±5.92)h-1、消除速率常数(β)为(0.15±0.03)h-1、体清除率(Cl)为(216.06±52.98)mL/h/kg。速度法计算得到的多西环素的药物动力学参数如下:β为(0.13±0.02)h-1、肾排泄速度常数(ke)为(0.08±0.02)h-1、肾清除率(Clre)为(113.35±18.02)mL/h/kg、肝清除率(Clhe)为(102.71±32.14)mL/h/kg。研究结果表明,多西环素在大鼠体内分布广泛、消除缓慢;此外,大鼠体内多西环素的消除过程中,肝脏和肾脏均发挥了主要作用,且二者作用相当。Seven healthy adult male Wistar rats, with an average weight of 250 g, were used to study the pharmacokinetics characteristics of doxycycline in plasma and urine after intravenous administration at 10 mg/kg. The doxycycline concentrations in plasma and urine samples were determind by a high performance liquid chromatography method. Then the plasma concentrations versus time data were subjected to compartmental analysis to obtain its pharmacokinetics parameters in plasma, while rate method was used to calculate the pharmacokinetics parameters in urine. The disposition of doxycycline after single intrave- nous injection was best described by a two-compartment open model. And the main plasma pharmacokinetics parameters were as flows： the volume of distribution （Va） was （1493.48±243.65） mL/kg, distribution rate constant （a） was （13.70±5.92） h-1 , elimination rate constant （[3） was （0.15±0.03） h -1, and body clearence （CI） was （216.06：k52.98） mL/h/kg. The pharmaeokinetics parameters of doxcycline derived from rate method were listed below： 13 was （0.13±0.02） h-1 , renal excretion rate constant （ko） was （0.08±0.02） h-1, renal clearence （Clre） was （113.35±18.02） mL/h/kg, and hepatic clearence （Clhe） was （102. 71± 32. 14） mL/h/kg. In conclusion, doxycycline was distributed extensively and eliminated slowly in rats after intravenous administration. Liver and kidney shared the same abilities for elimination of doxcycline from rats.

关 键 词：多西环素 大鼠 血浆 尿液 药物动力学 

分 类 号：S859.796[农业科学—临床兽医学]