肌注马波沙星在犊黄牛体内的药动学及半体内抗菌后效应研究

Pharmacokinetic of Marbofloxacin in Infancy Yellow Cattle after Single Intramuscular Administrations and ex vivo the Post-antibiotic Effects

旨在研究单次肌内注射马波沙星在犊黄牛体内的药动学及马波沙星对多杀性巴氏杆菌的抗菌后效应。选用5头健康犊黄牛按体重以2mg·kg-1的剂量给药,用高效液相色谱法测定马波沙星的血药浓度,使用WinNolin6.2药物动力学软件提供的非房室模型处理血药浓度-时间数据。并测定马波沙星对多杀性巴氏杆菌在预定时间点收集血清中的抗菌后效应(PAE)。马波沙星在犊牛血清中的主要药动学参数:Cmax2.04μg·mL-1、Tmax0.83h、AUC15.03h·μg·mL-1、AUMC138.67h·h·μg·mL-1、MRT9.17h、t1/2β9.00h、Vd1.80L·kg-1、CL/F0.14L·(h·kg)-1。当血清中马波沙星浓度大约在2MIC、4MIC、8MIC时,其PAE的值分别为1.90、2.65、3.50h。结果表明,犊牛肌注马波沙星后,吸收相对较为迅速,分布广泛,消除缓慢;对多杀性巴氏杆菌在血清中具有较长的抗菌后效应,且与暴露药物呈明显的浓度依赖性。

This experiment was conducted to study the pharmacokinetics parameters of marbofloxacin after single intramuscular administration in infancy yellow cattle and the Post-antibiotic effects(PAE)of marbofloxacin against Pasteurella multocida in serum.Marbofloxacin was administered to 5healthy infancy yellow cattle at a dose of 2mg·kg-1 of body weight,the concentrations of marbofloxacin in serum were determined by high-performance liquid chromatography and marbofloxacin concentration-time data in serum were analyzed using non-compartmental analysis of WinNolin6.2programme.Furthermore,PAE of marbofloxacin against Pasteurella multocida were tested in serum collected at predetermined time point.The main pharmacokinetic parameters intramuscularly were as follows:Cmax=2.04μg·mL-1,Tmax=0.83 h,AUC=15.03h·μg·mL-1,AUMC =138.67h·h·μg·mL-1,MRT =9.17 h,t1/2β=9.00 h,Vd=1.80L·kg-1,CL/F= 0.14L·(h·kg)-1.The PAE of marbofloxacin against P.multocida at the concentration levels of 2MIC,4MIC,8MIC in serum were 1.90,2.65,3.50 hrespectively.It was noted that marbofloxacin was relatively rapidly absorbed,widely distributed and slowly eliminated after intramuscular administration.The PAE of marbofloxacin against P.multocidain serum wasobviously prolonged and dependent on concentration.