甲砜霉素在感染多杀性巴氏杆菌鸡体内的药物动力学

Pharmacokinetics of thiamphenicol in experimentally infected chickens with Past-eurella multocida

30只健康杂交肉鸡随机分成3组,每组10只,雌雄各半,分别进行健康鸡静脉注射、健康和巴氏杆菌感染鸡口服给药的药动学研究。静注和口服的给药剂量按体质量分别为15mg/kg和30mg/kg。以反相HPLC测定血浆中甲砜霉素的质量浓度,药物浓度-时间数据用3P97药动学程序软件处理。健康鸡单剂量静注给药后,血药浓度-时间数据符合无吸收二室开放模型,其主要动力学参数分别为:V(c)为(0.58±0.09)L/kg,t1/2α(0.11±0.03)h,t1/2β(0.95±0.18)h,AUC为(11.99±0.90)mg/(L.h),CL(s)为(1.26±0.10)L/(kg.h)。健康鸡和巴氏杆菌感染鸡单剂量口服给药血药浓度-时间数据均符合一级吸收一室开放模型。健康鸡口服给药的主要动力学参数分别为:Lagtime(0.04±0.02)h,t1/2ka(0.16±0.08)h,t1/2ke(1.64±0.22)h,T(peak)(0.57±0.18)h,C(max)(6.34±0.56)mg/L,AUC为(19.02±1.48)mg/(L.h),F为79.32%。巴氏杆菌感染鸡口服给药的主要动力学参数分别为:Lagtime(0.07±0.02)h,t1/2ka(0.54±0.26)h,t1/2ke(1.74±0.27)h,T(peak)(1.31±0.39)h,C(max)(5.28±0.73)mg/L,AUC为(21.75±1.03)mg/(L.h),F90.70%。与健康鸡相比,甲砜霉素在感染鸡的t1/2(ka)、T(peak)和Lag-time显著延长(P<0.05或P<0.01),且比健康鸡具有更高的生物利用度。但甲砜霉素在巴氏杆菌感染鸡体内的消除速度未受影响。

Thirty healthy chickens were randomly divided into three groups.The pharmacokinetics of thiamphenicol were investigated following single intravenous （15 mg/kg b.w.）,and oral （30 mg/kg b.w.） administration in healthy chickens experimentally infected with Pasteurella multocida.Blood samples were collected at different intervals after administration of thiamphenicol.The thiamphenicol in plasma was extracted with and de-proteined by ethyl acetate and its concentrations in plasma were determined by high performance liquid chromatography （HPLC） with a limit of detection of 0.01 mg/L.The concentration-time data of thiamphenicol in plasma were analyzed with pharmacokinetic compartment analysis soft （3P97）.The concentration-time data of thiamphenicol after i.v.administration were fitted to a two-compartment open model.The main pharmacokinetic parameters were as follows：V（c）（0.58±0.09） L/kg,t1/2α（0.11±0.03） h,t1/2β（0.95±0.18） h,AUC（11.99±0.90） mg/（L·h）,CL（s） （1.26±0.10） L/（kg·h）.The concentration-time data after oral adminstration in healthy and infected chicken were fitted to a one-compartment open model with first-order absorption.The main pharmacokinetic parameters in healthy chicken were as follows： lagtime（0.04±0.02） h,t1/2ka（0.16±0.08） h,t1/2ke（1.64±0.22） h,T（peak）（0.57±0.18） h,C（max）（6.34±0.56） mg/L,AUC （19.02±1.48） mg/（L·h）,F 79.32%.The main pharmacokinetic in infected chicken parameters were as follows：lagtime 0.07±0.02 h,t1/2ka（0.54±0.26） h,t1/2ke（1.74±0.27） h,T（peak）（1.31±0.39） h,C（max）（5.28±0.73） mg/L,AUC（21.75±1.03） mg/（L·h）,F 90.70%.The results showed that thiamphenicol was completely absorbed by the oral routes in chicken infected with Pasteurella multocida,but the pharmacokinetic parameters of t1/2（ka）,T（peak） and lagtime were significantly lengthened（P0.05 or 0.01）.