关键词：
盐酸多西环素;黄颡鱼;维氏气单胞菌;药代动力学;药效学
摘 要：
为探明盐酸多西环素治疗黄颡鱼维氏气单胞菌感染的防耐药给药方案,体外测定盐酸多西环素对维氏气单胞菌的最小抑菌质量浓度、最小杀菌质量浓度、防耐药突变质量浓度、耐药选择窗以及抗菌后效应等药效学参数,并根据国标渔药盐酸多西环素的使用方案,在水温(20±2)℃下,体质量(200±50)g的黄颡鱼口灌20 mg/kg的盐酸多西环素,给药后0.5、1、2、4、8、12、24、48、78 h取血、肌肉、脑组织、肝胰脏、肾脏样品,利用高效液相色谱法测定和分析盐酸多西环素在黄颡鱼体内5个组织的药代动力学参数.试验结果显示,盐酸多西环素对维氏气单胞菌的最小抑菌质量浓度为0.5μg/mL,最小杀菌质量浓度为1.0μg/mL,防耐药突变质量浓度为4.0μg/mL,耐药选择窗为0.5~4.0μg/mL,抗菌后效应分别为(0.95±0.24)、(0.79±0.58)、(1.92±0.71)h.黄颡鱼口灌20 mg/kg的盐酸多西环素后,血清、肝胰脏、肾脏、肌肉、脑中的曲线下面积(0~78 h)与最小抑菌质量浓度的比值(AUC0~78h/MIC)分别为75.5580、686.5486、557.2362、736.9682、234.9658,最大药物质量浓度与最小抑菌质量浓度的比值(ρmax/MIC)为2.4908、18.6652、15.3044、24.1590、10.9018.根据浓度依赖型药物曲线下面积(0~t)与最小抑菌质量浓度的比值(AUC0~t/MIC)>125、最大药物质量浓度与最小抑菌质量浓度的比值(ρmax/MIC)>8的有效标准,确定盐酸多西环素用药方案为20 mg/kg,每日1次.依据肌肉中的药物残留动力学数据,确定休药期至少11.2 d.综合药代动力学参数和药效学参数,试验结果可为利用国标渔药盐酸多西环素有效治疗黄颡鱼维氏气单胞菌感染提供理论依据.
译 名：
Treatment Regimen of Doxycycline Hydrochloride for Aeromonas veronii Infection in Yellow Catfish Pelteobagrus fulvidraco
单 位：
National Aquatic Animal Pathogen Bank,Shanghai Ocean University,Shanghai 201306,China;Key Laboratory of Freshwater Aquatic Germplasm Resources,Ministry of Agriculture and Rural Affairs,Shanghai Ocean University,Shanghai 201306,China;National Experimental Teaching Demonstration Center for Fishery Sciences,Shanghai Ocean University,Shanghai 201306,China
关键词：
doxycycline hydrochloride%Pelteobagrus fulvidraco%Aeromonas veronii%pharmacokinetics%pharmacodynamics
摘 要：
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 0.5μg/mL,the minimum bactericidal concentration of 1μg/mL,the anti-drug mutation concentration of 4μg/mL,the drug resistance selection window of 0.5-4.0μg/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,AUC 0~78 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,andρmax/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 andρmax/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.
