猪半体内氟苯尼考对大肠杆菌的药动学-药效学同步关系研究

Pharmacokinetics/Pharmacodynamics Integration of Florfenicol against E.coli in Pigs ex vivo

采用体内药动学和体外药效学联合的方法,研究氟苯尼考在猪半体内抗大肠杆菌的活性,为合理应用氟苯尼考治疗猪大肠杆菌病提供参考。氟苯尼考在MH肉汤及血清中对猪大肠杆菌的最小抑菌浓度(MIC)分别为3.25和8.75μg.mL-1。猪按20 mg.kg-1的剂量肌内注射氟苯尼考后,药物吸收缓慢且不规则,血浆药物达峰时间为(3.60±1.52)h,峰浓度为(5.28±1.48)μg.mL-1。氟苯尼考在猪体内消除缓慢,体内平均滞留时间为(26.61±9.81)h,消除半衰期为(17.49±8.04)h。半效浓度参数(EC50)为(7.76±4.53)h。AUC0→24h/MIC为(7.69±1.48)h,Cmax/MIC为(0.60±0.17)。由于大肠杆菌对氟苯尼考的敏感性较差和氟苯尼考肌内注射药动学特征的限制,应用氟苯尼考,按照常规方案治疗猪大肠杆菌病,可能导致治疗失败。

For the rational usage of florfenicol to treat the colibacillosis of pigs,the integration of pharmacokinetics in vivo and pharmacodynamics in vitro was used to study the antibacterial activity of {lorfenicol against E. coli in pig serum ex vivo. The accurate MIC of florfenicol against E. coli in MH broth and serum was 3.25 and 8. 75μg[mL^-1, respectively. Florfenicol was absorbed slowly and anomaly in pigs after intramuscular administration（20 mg·kg^-1）. The Cmax was （5.28±1.48） μg · mL^-1 at （3.60±1.52） h. The elimination of florfenicol was slow in pigs. Mean residence time（MRT） was （26.61± 9.81） h. Elimination half-life（t1/2β） was （17.49±8.04） h. EC50 was （7.76±4.53） h. AUC0→24/MIC was （7.69±1.48） h and Cmax/MIC was （0.60 ±0.17）. Because of the poor activity of florfenicol against E. coli and the lower plasma Cmax Of florfenicol in pigs, it may fail to get desirable treatment result when curing the infection of E. coli in pigs by the routine regimen.