抗菌新兽药“菌灭”在兔体内的动力学研究

Pharmacokinetics of Junmie for Novel Antibacterial Medicine in Rabbit

[目的]研究"菌灭"在健康兔体内的药物动力学规律,为该药的合理应用提供依据。[方法]以苯甲酰环丙沙星为内标,建立检测菌灭浓度的HPLC方法。给健康家兔分别静脉注射和肌肉注射菌灭,按照所建立的HPLC方法检测注射后血浆菌灭浓度的变化,选定最佳药代动力学模型。[结果]所建立的HPLC条件:流动相为100 ml 60%(V/V)的甲醇溶液(pH 3.0);流速1.0 ml/min;柱温:(25.0±0.5)℃;检测波长:278 nm。静脉注射和肌肉注射的兔血样的血样药时数据分别符合一级吸收二室和一室开放模型,其血样中主要药动学参数,静脉注射:T1/2α=0.07 h,T1/2β=0.82 h,AUC=3.51 mg/(L.h),CLB=4.57 L/(mg.h);肌肉注射:T1/2Kα=0.33 h,T1/2K=0.33 h,Tp=0.6 h,Cmax=2.55μg/ml,AUC=4.87 mg/(L.h),生物利用度约为110%。[结论]菌灭经肌肉给药吸收快,生物利用度高,分布广泛,消除快。

[Objective] The paper presents the pharmacokinetics of Junmie in healthy rabbits and thus provides a basis for its rational application.[Method] HPLC method was developed to detect the concentration of Junmie with benzoyl ciprofloxacin as internal standard. After the healthy rabbits was respectively injected Junmie intravenously or intramuscularly, plasma concentration after injection was detected with the established HPLC method so as to determine the best pharmacokinetic model. [Result] The conditions of HPLC were as follows： mobile phase was 100 ml 60% （V/V） methanol solution （pH 3.0） ; flow rate was 1.0 ml/min ; column temperature was（25.0±0.5）℃; detection wave-length was 278 nm. The concentration-time data of the plasma, collected from intravenously and intramuscularly injected rabbits, was sepa- rately in line with the two compartments and one compartment open model with the first order absorption. The main pharmacokinetie parameters of the plasma sample （i.v.） were as below： T1/2α= 0.07 h, T1/2β= 0.82 h, AUC = 3.51 mg/（L·h）, CLB = 4.57 L/（mg·h）; the plasma sample （i.m.） ： T1/2κα=0.33 h, T1/2κ=0.33 h, Tp=0.6 h, Cmax=2.55μg/ml, AUC = 4.87 mg/（L·h）. The bioavail- ability was approximately 110%. [ Conclusion] After intramuscular administration, Junmie is absorbed and eliminated quickly with high bioavailability and extensive distribution