盐酸头孢噻呋注射液在猪体内的比较药动学研究

doi:10.16431/j.cnki.1671-7236.2021.04.036

摘要/Abstract

摘要： 本研究采用肺部支气管灌流技术对盐酸头孢噻呋注射液在健康猪和患巴氏杆菌病的感染猪体内的药动学特征进行了比较，为指导盐酸头孢噻呋注射液治疗猪巴氏杆菌病提供临床数据支持。选取12头健康仔猪，随机均分为健康组和感染组。感染组通过人工感染多杀性巴氏杆菌建立疾病模型。2组动物分别按交叉试验设计，肌内注射盐酸头孢噻呋注射液，在不同时间点采集血液和支气管肺泡灌洗液，用高效液相色谱法（HPLC）检测头孢噻呋含量。健康猪血浆及支气管肺泡灌洗液中的药峰浓度（C_max）分别为22.33和2.49 μg/mL，相差近9倍；消除半衰期（T_1/2）分别为19.51和70.19 h，在肺部的消除非常缓慢，时长是血浆的3.6倍；药-时曲线下面积（AUC_0-∞）分别为372.05和94.59 μg·h/mL；表观分布容积（Vd/F）分别为0.41和5.24 L/kg，头孢噻呋与肺脏呈现高度结合。感染组血浆及支气管肺泡液C_max分别为11.81和5.05 μg/mL，T_1/2分别为11.79和24.65 h，AUC_0-∞分别为162.65和29.73 μg·h/mL，Vd/F分别为0.53和4.65 L/kg，与健康组表现出相同的特点。结果表明，盐酸头孢噻呋注射液在猪体内具有吸收迅速，消除缓慢，生物利用度高的药代动力学特点，且其在血浆和支气管肺泡灌洗液中的药动学参数存在显著差异。

关键词: 盐酸头孢噻呋注射液; 药代动力学; 猪; 血浆

Abstract: In this study,the pharmacokinetic (PK) of ceftiofur hydrochloride injection in healthy pigs and infected pigs with pasteurellosis was studied by lung bronchialperfusion technique.Twelve piglets were randomly averagely divided into healthy and infection groups.The infection group was artificially infected with Pasteurella multocida to establish the disease model.Two groups of pigs were intramuscularly injected with ceftiofur hydrochloride injection according to the cross-experiment design.Blood and bronchoalveolar lavage fluid (BALF) were collected at different time points,and the drug content was detected by HPLC.The main PK parameters in plasma and BALF of healthy pigs were as follows:Drug peak concentration (C_max) were 22.33 and 2.49 μg/mL,respectively,the difference was nearly 9 times;Elimination half-life (T_1/2) were 19.51 and 70.19 h,respectively,the elimination in lung was very slow,which was 3.6 times longer than that in plasma;Area under the concentration-time curve (AUC_0-∞) were 372.05 and 94.59 μg·h/mL,respectively;Apparent distribution volume (Vd/F) were 0.41 and 5.24 L/kg,respectively,ceftiofur showed highly combined with lung.The corresponding PK parameters in infection groups were as follow:C_max were 11.81 and 5.05 μg/mL respectively;T_1/2 were 11.79 and 24.65 h,respectively;AUC_0-∞ were 162.65 and 29.73 μg·h/mL respectively;Vd/F were 0.53 and 4.65 L/kg,respectively.It showed the same characteristics as the healthy group.The results showed that ceftiofur hydrochloride injection had the PK characteristics of rapid absorption,slow elimination and high bioavailability in pigs,and there were significant differences in PK parameters between plasma and BALF.

Key words: ceftiofur hydrochloride injection; pharmacokinetic; pigs; plasma

中图分类号:

S859.7

蒲善菊, 黄玲利, 米坤, 孙达, 王涵宇, 潘源虎, 刘振利. 盐酸头孢噻呋注射液在猪体内的比较药动学研究[J]. 中国畜牧兽医, 2021, 48(4): 1472-1481.

PU Shanju, HUANG Lingli, MI Kun, SUN Da, WANG Hanyu, PAN Yuanhu, LIU Zhenli. Comparative Pharmacokinetics of Ceftiofur Hydrochloride Injection in Pigs[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(4): 1472-1481.

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