环糊精包合氟苯尼考在猪体内的药代动力学研究

为评价采用新包被工艺生产的氟苯尼考（受试制剂F）与国外同类产品（R1）、国内同类产品（R2）在猪体内的生物等效性并探索其药代动力学特性，本试验采用随机三制剂、三周期自身交叉试验设计，选取6头健康的阉割小公猪（体重15 kg±2 kg），分别灌胃给药3种制剂，给药剂量为20 mg/（kg·BW），采用高效液相色谱法测定血浆中氟苯尼考浓度，利用Kinetica 5.0软件分析药代动力学特性，SAS统计软件进行生物等效性评价。结果显示，受试制剂在猪体内的药时曲线符合带时滞的一级吸收一室开放模型，F、R1、R2的峰浓度（C_max）分别为16.0845、18.3287和21.1678 μg/mL，药物达峰时间（T_max）分别为5.0、1.9、1.5 h；药-时曲线下面积_（0-∞）（AUC_0-∞）分别为144.7327、118.2670和123.3715 μg/mL·h；受试制剂相比于两种参比制剂的相对生物利用度分别为122.51%（R1）和117.52%（R2）。结果表明，环糊精包被氟苯尼考有更好的缓释作用，具有更好的生物安全性，药效维持时间长，生物利用度有效提高。

Study on Pharmacokinetics of Cyclodextrin-encapsulated Flufenicol in Pigs

In order to evaluate the bioequivalence of flufenicol (test reagent F) produced by the new coating process with the similar foreign products (R1) and domestic products (R2),and to explore its pharmacokinetic characteristics in pigs.The design of random triplet and triplet self-crossing test was adopted.Six healthy castrated male pigs (15 kg±2 kg) were respectively to take three formulations by oral administration (20 mg/kg).Flufenicol plasma concentration was analyzed by high performance liquid chromatography.Pharmacokinetic characteristics were analyzed by Kinetica 5.0,and bioequivalence was evaluated by SAS statistical software.The results showed that the drug time curve of the tested preparation in pigs conformd to the first-order absorption one-chamber open model.The C_max of F,R1 and R2 were 16.0845,18.3287 and 21.1678 μg/mL respectively,T_max were 5.0,1.9 and 1.5 h respectively;AUC_0-∞ were 144.7327,118.2670 and 123.3715 μg/mL·h,respectively.The relative bioavailability of the two reference preparations was 122.51% (R1) and 117.52% (R2),respectively.The results showed that cyclodextrin coated with flurbenicol had better sustained-release effect,better biosafety,longer duration of efficacy,and higher bioavailability.