新型氟苯尼考药丸的制备及其在大黄鱼体内的药代动力学分析

Fabrication and in vivo pharmacokinetics of an antibiotic florfenicol pill towards applying in Pseudosciaena crocea fishery

大黄鱼养殖业中存在因过量用药而造成环境污染严重及大黄鱼发病率和死亡率高等问题,以淀粉、壳聚糖和明胶三元复合物作为载体,以渔业中应用较多的广谱抗生素氟苯尼考为药物模型,制备了一种可生物降解并可定量给药的抗生素药丸。采用扫描电子显微镜、高效液相色谱法等手段对该药丸的物理特性、吸水性能、抑菌性能及药物残留量进行了检测。结果表明:所制备的载体和药丸具有一致的内部微观结构,多孔结构分布均匀,孔与孔之间具有良好的连通性,有利于药物的流通和释放。体外抑菌试验结果显示,其抑菌能力与氟苯尼考的含量成正相关。经口服药丸后,氟苯尼考在大黄鱼血液、肝脏和肌肉中的药代动力学符合一级吸收二室开放模型的特征,并可在血液、肝脏和肌肉中缓慢消解。

Problems such as drug abusiveness, poor efficacy, nonquantitatively medicine and improper administration raised high morbidity and mortality in Pseudosciaena crocea fishery. A biodegradable antibiotic pill was manufactured, in which starch, chitosan and gelatin were used as carriers and florfenicol, a broad spectrum antibiotic in fishery, was used as the model drug. The carrier＇s morphology, water uptake, bacteriostasis capability and drug-residue of the pill were analyzed using scanning electron microscopy （ SEM） , high performance liquid chromatography （ HPLC） , in vitro and in vivo test. The microscopic structures of both carrier and pill were quite uniform in pore size and pore distribution with good interconnectivity between pores, which is favorable for the drug＇s circulation and release. The in vitro bacteriostasis test showed that the pills were effective against Vibrio alginolyticuswhile the carrier materials were little antimicrobial active. The in vivo toxicity, pharmacokinetics and drug residues as a function of time were tested with Pseudosciaena crocea as the test fish. The blood, liver and muscle of tested fishes were obtained and evaluated. The results showed that the carrier materials were low toxic for Pseudosciaena crocea. 5 -7 days after oral administration, trace level residue of florfenicol was tested in blood, liver and muscle tissue of Pseudosciaena crocea. The pharmacokinetics was in line with a two-compartment open model with first-order absorption factor.