不同水温下盐酸氯苯胍在斑点叉尾鮰血浆的药代动力学研究

doi:10.3969/j.issn.1004-1524.2018.10.04

浙江农业学报 ›› 2018, Vol. 30 ›› Issue (10): 1640-1646.DOI: 10.3969/j.issn.1004-1524.2018.10.04

不同水温下盐酸氯苯胍在斑点叉尾鮰血浆的药代动力学研究

余琳雪^{1, 2}, 刘永涛^{2, 3}, 苏志俊^{1, 2}, 丁浩^{1, 2}, 艾晓辉^{2, 3, *}

1.水产科学国家级实验教学示范中心(上海海洋大学),上海 201306;
2.中国水产科学研究院长江水产研究所,湖北武汉430223;
3.农业农村部水产品质量安全控制重点实验室,湖北武汉430223

收稿日期:2017-12-12 出版日期:2018-10-25 发布日期:2018-11-02
通讯作者: 艾晓辉,E-mail:aixh@yfi.ac.cn
作者简介:余琳雪(1992—),女,湖北襄阳人,硕士研究生,主要从事水产动物药理学及药残控制技术研究。E-mail:yulx92@126.com
基金资助:
中国水产科学研究院基本科研业务费(2016HY-ZD1202,2018JBF02)

Pharmacokinetics of robenidine hydrochloride in plasma of channel catfish (Ictalurus punctatus) at different water temperatures

YU Linxue^{1, 2}, LIU Yongtao^{2, 3}, SU Zhijun^{1, 2}, DING Hao^{1, 2}, AI Xiaohui^{2, 3, *}

1. National Demonstration Center for Experimental Fisheries Science Education,Shanghai Ocean University, Shanghai 201306, China;
2. Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China;
3. Key Labrotary of Control of Quality and Safety for Aquatic Products, Ministry of Agriculture and Rural Affairs, Wuhan 430223, China

Received:2017-12-12 Online:2018-10-25 Published:2018-11-02

摘要/Abstract

摘要： 研究不同水温(18、28 ℃)条件下盐酸氯苯胍(robenidine hydrochloride,ROBH)在斑点叉尾鮰(Ictalurus punctatus)血浆的药代动力学特征。以20 mg·kg^-1体质量剂量的盐酸氯苯胍单次口灌斑点叉尾鮰,采用高效液相色谱-串联质谱法测定血浆中盐酸氯苯胍的浓度,内标法定量,并采用3p97药代动力学软件计算药代动力学参数、开展模型分析。结果表明,在不同水温条件下盐酸氯苯胍在斑点叉尾鮰血浆的药时曲线均符合二室模型特征,动力学方程分别为C_{18 ℃}=4.17e^-0.01t+2.48e^-0.008^t-6.65e^-0.05^t和C_{28 ℃}=7.69e^-0.02t+0.13e^-0.01t+-7.82e^-0.27^t。血浆中盐酸氯苯胍达峰时间T_peak 分别为42.36和10.03 h,峰浓度值C_max分别为3.51和5.76 μg·mL^-1,表观分布容积V/F(c)分别为3.79和2.78 L·kg^-1,分布相的一级速率常数α分别为0.248和0.222 h^-1,消除相的一级速率常数β分别为0.006和0.007 h^-1,吸收半衰期T_1/2(_ka₎分别为14.67和2.54 h,消除半衰期T_1/2(_β₎ 分别为85.52和58.63 h,中央室向周边室转运的一级速率常数K₁₂分别为0.000 2和0.000 2 h^-1,周边室向中央室转运的一级速率常数K₂₁分别为0.009和0.01 h^-1,药-时曲线下面积分别为554.18和326.74 μg·mL^-1·h^-1。研究结果表明,盐酸氯苯胍在斑点叉尾鮰体血浆的吸收、分布和消除受水温的影响显著,高水温条件下盐酸氯苯胍的达峰时间短,峰浓度值约是低水温时的2倍,水温对血药曲线下面积的影响较大,对肾清除率影响不大。研究结果为盐酸氯苯胍在斑点叉尾鮰养殖过程中不同季节的合理使用提供一定理论依据。

关键词: 盐酸氯苯胍, 斑点叉尾鮰, 药代动力学, 水温

Abstract: The pharmacokinetics of robenidine hydrochloride in the plasma of channel catfish (Ictalurus punctatus) at different water temperatures (18, 28 ℃) were investigated in this study.The concentration of robenidine hydrochloride in the plasma of channel catfish was determined by HPLC-MS. Pharmacokinetic parameters were calculated by using the 3p97 Practical Pharmacokinetic Program software. The concentration-time data of robenidine hydrochloride in plasma were fitted to a two-compartment model at both 18 ℃ and 28 ℃ water temperature. The kinetic equations were C_{18 ℃}=4.17e^-0.01^t+2.48e^-0.008^t-6.65e^-0.05^t, C_{28 ℃}=7.69e^-0.02^t+0.13e^-0.01^t-7.82e^-0.27^t, respectively. The major pharmacokinetic parameters at water temperature 18 ℃ and 28 ℃ were as follows: The time point of maximum plasma concentration (T_peak) was 42.36 and 10.03 h, respectively, peak plasma concentration (C_max) was 3.51 and 5.76 μg·mL^-1, respectively. Relatively apparent distributed volume V/F(c) was approached to 3.79 and 2.78 L·kg^-1, respectively. The distribution rate constant α was 0.248 and 0.222 h^-1, respectively. The elimination rate constant β was 0.006 and 0.007 h^-1, respectively. The absorption half-time [T_1/2(_ka₎] was 14.67 and 2.54 h, respectively. The elimination half-time [T_1/2(_β₎] was 85.52 and 58.63 h, respectively. First-order rate constant for drug distributions from central compartment to peripheral compartment (K₁₂) was 0.000 2 and 0.000 2 h^-1,respectively. First-order rate constant for drug distributions from peripheral compartment to central compartment (K₂₁) was 0.009 and 0.01 h^-1, respectively. The areas under the curve was 554.18 and 326.74 μg·mL^-1·h^-1, respectively. The results showed that the temperature could significantly affect the absorption, distribution and elimination of robenidine hydrochloride in the plasma of channel catfish. Under high water temperature, the peak time of robenidine hydrochloride was short, the peak concentration value was about twice of that at low water temperature, and the water temperature had a greater influence on the areas under the curve, but had little influence on the renal clearance rate. It also provided a theoretical basis for the rational use of robenidine hydrochloride in channel catfish farming during different seasons.

Key words: robenidine hydrochloride, channel catfish (Ictalurus punctatus), pharmakokinetic, water temperature

中图分类号:

S948

余琳雪, 刘永涛, 苏志俊, 丁浩, 艾晓辉. 不同水温下盐酸氯苯胍在斑点叉尾鮰血浆的药代动力学研究[J]. 浙江农业学报, 2018, 30(10): 1640-1646.

YU Linxue, LIU Yongtao, SU Zhijun, DING Hao, AI Xiaohui. Pharmacokinetics of robenidine hydrochloride in plasma of channel catfish (Ictalurus punctatus) at different water temperatures[J]. , 2018, 30(10): 1640-1646.

参考文献

[1] 曾勇. 动物性食品中氯苯胍和左旋咪唑残留检测方法研究[D].武汉:华中农业大学,2008.
ZENG Y.Development of methods for determination of robenidine and levamisole residues in animal derive food [D]. Wuhan: Huazhong Agricultural University, 2008.(in Chinese with English abstract)
[2] 农业部兽药评审中心.兽药国家标准汇编:兽药地方标准上升国家标准(第一册)[M]. 北京:中国农业出版社,2010:189.
[3] 刘勇军,吴银良,姜艳彬.高效液相色谱法测定鸡组织与鸡蛋中的盐酸氯苯胍的残留量[J].色谱,2010,28(9):905-907.
LIU Y J, WU Y L, JIANG Y B.Determination of robenidine residue in chicken tissues and eggs by high performance liquid chromatography[J]. Chinese Journal of Chromatography, 2010, 28(9):905-907.(in Chinese with English abstract)
[4] DOWLING G, O'KEEFFE M, SMYTH M R. Determination of robenidine in eggs by liquid chromatography with UV spectrophotometric detection[J]. Analytica Chimica Acta, 2005, 539(1/2):31-34.
[5] YEOM H, YANG D H, SUH J H, et al.Determination of robenidine residues in chicken muscle by high performance liquid chromatography with ultraviolet detection[J]. Archives of Pharmacal Research, 2013, 36(3):359-365.
[6] 李慧素,吴宁鹏,班付国,等.超高效液相色谱-串联质谱法测定鸡组织中氯苯胍残留[J].中国兽药杂志,2012,46(9):26-29.
LI H S, WU N P, BAN F G, et al.Determination of robenidine residue in chicken tissues by ultra performance liquid chromatography-tandem mass spectrometry[J]. Chinese Journal of Veterinary Drug, 2012, 46(9):26-29.(in Chinese with English abstract)
[7] KOT-WASIK A, WASIK A.Determination of robenidine in animal feeds by liquid chromatography coupled with diode-array detection and mass spectrometry after accelerated solvent extraction[J]. Analytica Chimica Acta, 2005, 543(1/2):46-51.
[8] WILGA J, KOT-WASIK A, NAMIEŚNIK J. Comparison of extraction techniques of robenidine from poultry feed samples[J]. Talanta, 2007, 73(5):812-819.
[9] 吴仕辉,陈昆慈,戴晓欣,等.分散固相萃取/高效液相色谱法测定水产品中氯苯胍的残留量[J].分析测试学报,2011,30(12):356-1361.
WU S H, CHEN K C, DAI X X, et al.Determination of robenidine in fishery products by high performance liquid chromatography with dispersive solid phase extraction[J]. Journal of Instrumental Analysis, 2011, 30(12):1356-1361.(in Chinese with English abstract)
[10] 汤菊芬,蔡佳,廖建萌,等. HPLC-MS/MS 法同时测定水产品中的诺氟沙星、盐酸小檗碱、盐酸氯苯胍残留[J].中国兽药杂志,2014(8):55-60.
TANG J F, CAI J, LIAO J M, et al.Determination of norfloxacin, berberine hydrochloride and robenidine hydrochloride residues in aquatic products by high performance liquid chromatography-mass spectrometry(HPLC-MS/MS)[J]. Chinese Journal of Veterinary Drug, 2014(8):55-60.(in Chinese with English abstract)
[11] 汤菊芬,蔡佳,黄瑜,等.盐酸氯苯胍在红笛鲷体内的药代动力学及残留消除规律[J].广东海洋大学学报,2016,36(6):1-6.
TANG J F, CAI J, HUANG Y, et al.Pharmacokinetics and elimination regularity of robenidine hydrochloride residues in Luthjanus sanguineus[J]. Journal of Guangdong Ocean University, 2016, 36(6):1-6.(in Chinese with English abstract)
[12] 阮记明,胡鲲,章海鑫,等.两种水温条件下异育银鲫体内双氟沙星药代动力学比较[J].上海海洋大学学报,2011,20(6):858-865.
RUAN J M, HU K, ZHANG H X, et al.Pharmacokinetics comparisons of difloxacin in crucian carp(Carassais auratus gibebio) at two different water temperatures[J]. Journal of Shanghai Ocean University, 2011, 20(6): 858-865.(in Chinese with English abstract)
[13] 彭新亮,刘锦妮,何斌.不同水温下多西环素在草金鱼体内的药代动力学[J].畜牧与兽医,2014,46(6):83-86.
PENG X L, LIU J N, HE B.Pharmacokinetics of doxycycline in grass goldfish at different water temperatures[J].Animal Husbandry & Veterinary Medicine, 2014, 46(6):83-86.(in Chinese)
[14] 黄月雄,汤菊芬,简纪常,等.氟苯尼考在美国红鱼体内的药代动力学和组织分布[J].广东海洋大学学报, 2014, 34(3):58-64.
HUANG Y X, TANG J F, JIAN J C, et al.Tissues distribution and pharmacokinetics of florfenicol in sciaenops ocellatus[J]. Journal of Guangdong Ocean University, 2014, 34(3):58-64.(in Chinese with English abstract)
[15] FENG J, XU W, TAO X, et al.Simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in rat plasma by liquid chromatography tandem mass spectrometry and application in pharmacokinetic studies after oral administration of traditional chinese medicinal preparations containing scutellaria-coptis herb couple[J]. Journal of Pharmaceutical and Biomedical Analysis, 2010, 53(3):591-598.
[16] 王贤玉,宋洁,王伟利,等.氧氟沙星在吉富罗非鱼体内的药代动力学及残留的研究[J].大连海洋大学学报,2011,26(2):144-148.
WANG X Y, SONG J, WANG W L, et al.Pharmacokinetics and residues of ofloxacin in GIFT tilapia strain Oreochromis niloticus[J]. Journal of Dalian Ocean University,2011, 26(2):144-148.(in Chinese with English abstract)
[17] 李强,谢顺,曾松情,等.盐酸氯苯胍在兔体内的药动学及生物利用度研究[J].华南农业大学学报,2017,38(2):18-21.
LI Q, XIE S, ZENG S Q, et al.Studies on pharmacokinetic and bioavailability of robenidine hydrochloride in rabbits[J]. Journal of South China Agricultural University, 2017, 38(2):18-21.(in Chinese with English abstract)

不同水温下盐酸氯苯胍在斑点叉尾鮰血浆的药代动力学研究

Pharmacokinetics of robenidine hydrochloride in plasma of channel catfish (Ictalurus punctatus) at different water temperatures

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