中国农业科学 ›› 2018, Vol. 51 ›› Issue (19): 3807-3814.doi: 10.3864/j.issn.0578-1752.2018.19.017

• 畜牧·兽医·资源昆虫 • 上一篇    下一篇

泰地罗新注射液在猪体内的药动学及生物利用度研究

、闫超群1,黎健业1,张申1,谢顺1,胡浪1,顾欣2,曹莹2,黄士新2,黄显会1

 
  

  1. 1华南农业大学兽医学院/广东省兽药研制与安全评价重点实验室,广州 510642;2上海市动物疫病预防控制中心,上海201103
  • 收稿日期:2018-01-24 出版日期:2018-10-01 发布日期:2018-10-01
  • 通讯作者: 黄显会,Tel:020-87344801;E-mail:xhhuang@scau.edu.cn
  • 作者简介:闫超群,E-mail:1368268753@qq.com
  • 基金资助:
    十三五重点研发计划项目(2016YFD0501306)

Pharmacokinetics and Bioavailability of Tildipirosin Solution in Pigs

YAN ChaoQun1, LI JianYe1, ZHANG Shen1, XIE Shun1, HU Lang1, GU Xin2, CAO Ying2HUANG ShiXin2, HUANG XianHui1   

  1. 1Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation/College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642; 2 Shanghai Animal Disease Control Center, Shanghai 201103
  • Received:2018-01-24 Online:2018-10-01 Published:2018-10-01

摘要: 【目的】以健康猪为研究对象,开展泰地罗新注射液在猪体内的药动学特征及生物利用度的研究,从而为泰地罗新的临床应用提供科学依据。【方法】选取20头健康猪,随机分为2组,按4 mg·kg-1进行单次静注、肌注泰地罗新注射液,于注射后5 min、10 min、15 min、0.5 h、1 h、2 h、4 h、8 h、12 h、1 d、2 d、3 d、4 d、5 d、6 d、7 d、8 d、9 d、10 d、11 d、12 d、13 d、14 d、15 d进行前腔静脉采血,采用Phenomenex Luna C18(150 mm×2 mm,5 μm)。以乙腈-0.1%甲酸水溶液为流动相,梯度洗脱程序洗脱,流速0.25 mL·min-1,柱温为30℃,进样量 5.0 μL。样品自然解冻,准确吸取0.5 mL血浆于5 mL离心管内,加入2 mL乙腈,涡旋混匀,震荡10 min,8 000 r/min离心10 min,取上清液35℃下氮气吹干,1 mL复溶液复溶,过0.22 μm微孔滤膜,LC-MS/MS检测分析。泰地罗新在4—1 000 ng·mL-1 的浓度范围内呈现良好的线性关系,相关系数为0.994—0.998,检测限为2 ng·mL-1,定量限为4 ng·mL-1,该方法的相对回收率为87.91%—104.93%,呈良好的线性关系,相关系数为0.994—0.998。批内变异系数为2.12%—12.09%,批间变异系数3.92%—10.65%。该方法灵敏度高,操作简便,可以用于泰地罗新在猪体内的药代动力学研究。泰地罗新采用电喷雾离子源(ESI)离子化;正离子模式扫描;多反应监测模式(MRM),电喷雾电压(IS)为5500V;雾化气压力(GS1)为50psi;辅助气流速(GS2)为50 L·min-1,气帘气压力(CUR)为25 psi;离子源温度(TEM)为550 ℃;碰撞室压力(CAD)为6 psi。m/z→734.6/98.1和m/z→734.6/174.4。HPLC-MS/MS法检测猪血浆中泰地罗新的浓度。采用药动学软件 Winnonlin5.2.1的非房室模型分析方法,计算有关药物动力学参数。【结果】猪静脉注射给药后,AUClast和AUCinf(pred)分别为(18030.30±7560.75) h·ng·mL-1和(18795.31±7455.23) h·ng·mL-1。t1/2为(99.42±22.25) h,MRT为(81.71±12.15) h。肌肉注射给药后,Cmax为(886.00±155.63) ng·mL-1Tmax为(0.51±0.30)h,AUClast和AUCinf(pred)分别为(19702.05±6442.36)h·ng·mL-1和(20840.08±6849.76) h·ng·mL-1。t1/2为(100.83±20.23) hMRT为(81.80±9.44) h。绝对生物利用度为109.27%。【结论】泰地罗新肌注后在猪体内具有吸收迅速,分布广泛,达峰迅速,消除较慢,生物利用度高等特点,可在兽医临床上安全使用。

关键词: 泰地罗新, 药动学, 生物利用度,

Abstract: 【Objective】The aim of this study was to investigate the pharmacokinetic properties and bioavailability of tildipirosin in pigs after an intravenous or intramuscular administration of 4 mg·kg-1 body weight. 【Method】 Twenty healthy pigs were selected and randomly divided into 2 groups and received 4 mg·kg-1of tildipirosin injection by either intravenous or intramuscular administration. The blood was collected at 5 min, 10 min, 15 min, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d, 7 d, 8 d, 9 d, 10 d, 11 d, 12 d, 13 d, 14 d and 15 d after administration. Phenomenex Luna C18 (150 mm×2 mm, 5 μm) was used. Acetonitrile-0.1% formic acid aqueous solution was used as the mobile phase. The gradient elution procedure was used. The flow rate was 0.25 mL·min-1, the column temperature was 30, and the injection volume was 5.0 μL. The sample was thawed naturally, 0.5 mL of plasma was accurately pipetted into a 5 mL centrifuge tube, 2 mL of acetonitrile was added, vortexed and shaken for 10 min, centrifuged at 8000 r/min for 10 min. And then the supernatant was dried with nitrogen at 35 and reconstituted in 1 mL of solution. 0.22 μm microporous membrane, LC-MS/MS detection analysis. Tildipirosin showed a good linearity in the concentration range of 4-1000 ng·mL-1, with a correlation coefficient of 0.994-0.998, a detection limit of 2 ng·mL-1, and a limit of quantification of 4 ng·mL-1. The relative recovery rate of this method was 87.91%-104.93%, which showed a good linear relationship with the correlation coefficient of 0.994—0.998. The coefficient of intra-assay coefficient of variation was 2.12%—12.09%, and the inter-assay coefficient of variation was 3.92%—10.65%. The experimental method had high sensitivity and simple operation, and could be used for the pharmacokinetic study of tildipirosin in pigs. MS conditions of detection method: ESI ion source, positive ion scan, ion spray voltage: 5500V, TEM: 550, the pressure of CUR: 25 psi, the pressure of GS2 50L/min, the pressure of collision CAD: 6 psi. the quantitative ion is: tildipirosin m/z→735.1/98.0. Blood samples were collected and detected by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were estimated using the WinNonlin5.2.1 software package and SPSS 16.0 analysis of the time and concentration data.【Result】After intravenous injection, AUClast and AUCinf (pred) were (18030.30 ±7560.75) h·ng·mL-1 and (18795.31±7455.23) h·ng·mL-1, respectively;t1/2 was (99.42±22.25) h, and MRT was (81.71±12.15) h. After intramuscular injection, Cmax was (886.00±155.63) ng·mL-1; Tmax was (0.51 ± 0.30) h. AUClast and AUCinf (pred) were (19702.05±6442.36) h·ng·mL-1 and (20840.08±6849.76) h·ng·mL-1, respectively; t1/2 was (100.83±20.23) h and MRT was (81.80±9.44) h; the absolute bioavailability was 109.27%. 【Conclusion】 After intramuscular injection, the tildipirosin was absorbed quickly in pigs, distributed widely, peaked rapidly, and eliminated slowly.

Key words: tildipirosin, pharmacokinetic, bioavailability, pig