Abstract:To determine the dosage regimen of doxycycline hydrochloride (DH) in treatment of Aeromonas veronii infection in yellow catfish Pelteobagrus fulvidraco, the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), anti-drug mutation concentration (MPC), drug resistance selection window (MSW) and post antibacterial effect (PAE) of DH against A. veronii were determined in vitro. According to the application protocol of DH, yellow catfish with body weight of (200±50) g was administered orally by DH at a dose of 20 mg/kg at water temperature of (20±2) ℃, and samples of blood, muscle, brain, hepatopancreas and kidney were collected at 0.5, 1, 2, 4, 8, 12, 24, 48 and 78 h after administration for determination of the DH concentration in the tissues above by HPLC. The results showed that there was minimum inhibitory concentration of DH against A. veronii of 0.5 μg/mL, the minimum bactericidal concentration of 1 μg/mL, the anti-drug mutation concentration of 4 μg/mL, the drug resistance selection window of 0.5—4.0 μg/mL, and post antibacterial effect of (0.95±0.24), (0.79±0.58), (1.92±0.71) h, respectively. After oral administration of DH at a dose of 20 mg/kg, AUC0~78 h/MIC of 75.558 was observed in serum, 686.5486 in hepatopancreas, 557.2362 in kidney, 736.9682 in muscle and 234.9658 in brain, and ρmax/MIC of 2.4908 in serum, 18.6652 in hepatopancreas, 15.3044 in kidney, 24.159 in muscle and 10.9018 in brain. Based on the effective standard of concentration-dependent drug of AUC(0~t)/MIC>125 and ρmax/MIC>8 , the DH regimen with a dose of 20 mg/kg once a day led to effectively treat the infection of A. veronii in yellow catfish, and the withdrawal time for DH was at least 11.2 days. The finding provides a theoretical basis for the clinical rational use of DH in yellow catfish and the prevention and treatment of A. veronii infection in yellow catfish.
[1] 朱成科,向桢,叶华,等.黄颡鱼致病性维氏气单胞菌的分离鉴定[J].西南大学学报(自然科学版),2013,35(5):37-42. [2] 罗茵.《2020中国渔业统计年鉴》出版 广东水产品总产量首次全国第一[J].海洋与渔业,2020(6):12-13. [3] 崔利锋,农业农村部渔业渔政管理局,全国水产技术推广总站.2021中国水生动物卫生状况报告[M].北京:中国农业出版社,2021. [4] 康元环,张冬星,杨滨僮,等.维氏气单胞菌最新研究进展[J].中国人兽共患病学报,2018,34(5):452-459. [5] 付曼荃.黄颡鱼Hepcidin调节铁代谢对维氏气单胞菌生长的影响[D].武汉:华中农业大学,2021. [6] 黄聚杰.六种抗菌药物在花鲈体内的药代动力学及残留消除规律[D].厦门:集美大学,2016. [7] 邴晓菲,孙朋辉,王浩,等.盐酸多西环素临床治疗异育银鲫嗜水气单胞菌感染的给药方案的制定[J].淡水渔业,2016,46(2):45-49. [8] 梅清,喻婷,朱玉林,等.万古霉素单用及联合利福平或磷霉素对耐甲氧西林金黄色葡萄球菌防耐药突变浓度的研究[J].中国药理学通报,2011,27(7):944-947. [9] 崔俊昌,刘又宁,王睿,等.左氧氟沙星药代动力学/药效动力学参数与金黄色葡萄球菌耐药的相关性研究[J].中国临床药理学与治疗学,2007,12(9):989-992. [10] 刘远飞.氟喹诺酮类抗菌药后效应及其机制的研究[D].哈尔滨:东北农业大学,2002. [11] 丁俊仁,艾晓辉,汪开毓,等.强力霉素在斑点叉尾鮰体内药物动力学及残留消除规律研究[J].水生生物学报,2012,36(1):126-132. [12] 艾晓辉,丁运敏,汪开毓,等.在斑点叉尾鮰血清中强力霉素对嗜水气单胞菌药动-药效模型研究[J].水生生物学报,2011,35(6):893-899. [13] 王海娟,王利,苟小兰,等.鱼源维氏气单胞菌的耐药性研究[J].中国畜牧兽医,2013,40(8):159-164. [14] 王浩,权可艳,徐丽娟,等.恩诺沙星控制草鱼维氏气单胞菌的用药方案[J].淡水渔业,2013,43(2):48-53. [15] 李晓琳.抗菌药物的药动学和药效学参数对临床用药的意义[J].河北医药,2014,36(7):1079-1080. [16] 杨先乐,郑宗林.我国渔药使用现状、存在的问题及对策[J].上海水产大学学报,2007,16(4):374-380. [17] LIM J H, KIM M S, HWANG Y H, et al. Plasma and tissue depletion of florfenicol in olive flounder (Paralichthys olivaceus) after oral administration[J]. Aquaculture,2010,307(1/2):71-74. [18] 王金花.猪肌注盐酸多西环素的药物动力学和残留的研究[D].武汉:华中农业大学,2007. [19] 王群,孙修涛,刘德月,等.土霉素在黑鲷体内的药物代谢动力学研究[J].海洋水产研究,2001,22(1):42-47. [20] 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. [21] TOUTAIN P L. Pharmacokinetic/pharmacodynamic integration in drug development and dosage-regimen optimization for veterinary medicine[J]. The Academy of Pharmaceutical Sciences,2002,4(4):38. [22] 王睿.抗菌药物PK/PD参数对合理设计给药方案的意义[J].中国药师,2003,6(12):806-809. [23] KIM A, BANEVICIUS M A, NICOLAU D P. In vivo pharmacodynamic profiling of doripenem against Pseudomonas aeruginosa by simulating human exposures[J]. Antimicrobial Agents and Chemotherapy,2008,52(7):2497-2502. [24] BOWKER K E, NOEL A R, TOMASELLI S G, et al. Pharmacodynamics of the antibacterial effect of and emergence of resistance to doripenem in Pseudomonas aeruginosa and Acinetobacter baumannii in an in vitro pharmacokinetic model[J]. Antimicrobial Agents and Chemotherapy,2012,56(10):5009-5015. [25] 陈佰义.PK/PD理论指导下的优化抗菌治疗[J].中华临床感染病杂志,2009,2(2):69-70. [26] 房海,陈翠珍,张晓君,等.中华绒螯蟹病原维氏气单胞菌的检验[J].中国人兽共患病学报,2008,24(1):45-49. [27] 石焕阶.根据浓度依赖型与时间依赖型抗菌药物的特点制定给药方案[J].医药导报,2009,28(9):1222-1223.