在斑点叉尾血清中强力霉素对嗜水气单胞菌药动-药效模型研究  

STUDY ON PHARMACOKINETICS/PHARMACODYNAMICS MODEL OF DOXYCYCLINE AGAINST AEROMONAS HYDROPHILA IN SERUM OF CHANNEL CATFISH EX VIVO

作　　者：艾晓辉[1,2] 丁运敏[2,3] 汪开毓[1] 刘永涛[2] 沈丹怡[2,3] 

机构地区：[1]四川农业大学动物医学院,雅安625014 [2]中国水产科学研究院长江水产研究所,荆州434000 [3]华中农业大学水产学院,武汉430070

出　　处：《水生生物学报》2011年第6期893-899,共7页Acta Hydrobiologica Sinica

基　　金：农业部公益性行业科研专项“淡水鱼类出血性疾病综合防治技术集成与示范”(200803013)资助

摘　　要：为合理应用强力霉素治疗斑点叉尾(Ictalurus punctatus)细菌性败血症,采用体内药动学和体外药效学相结合的方法,研究了斑点叉尾血清中强力霉素抗嗜水气单胞菌(Aeromonas hydropila)的活性,数据使用3p97和kinetica4.4软件分析。结果表明:强力霉素在普通肉汤培养基和血清中对嗜水气单胞菌的最小抑菌浓度(MIC)均为2.0μg/mL。斑点叉尾按20 mg/kg体重的剂量口灌强力霉素后,药物吸收迅速、达峰快、消除缓慢,血浆药物达峰时间(Tmax)为2.57h,峰浓度(Cmax)为1.72μg/mL,消除半衰期[T(1/2)β]为38.63h。在半效应室内,半效浓度参数(EC50)为16.95h,即血清药物浓度为1.41μg/mL时可产生50%最大效应。PK-PD同步模型参数Cmax/MIC血清为0.86,AUC0→24h/MIC血清为20.57h。通过抑制效应的Sigmoid Emax模型方程可得到临床起到抑菌效果的最佳给药剂量范围为10.68—41.42 mg/kg体重。临床上发生斑点叉尾细菌性败血症时的最佳给药方案建议为:对出现临床病状的斑点叉尾以41.42 mg/kg体重的剂量进行拌饲投喂进行治疗,1次/d。临床上预防斑点叉尾细菌性败血症时以10.68 mg/kg体重的剂量进行拌饲投喂,1次/d。In order to determine reasonable dosage regimens of doxycycline in treating the haemorrhagic septicemia of channel catfish(Ictalurus punctatus),we integrated of pharmacokinetics in vivo and pharmacodynamics ex vivo to study the antibacterial activity of doxycycline against Aeromonas hydrophila in channel catfish serum.The minimum inhibitory concentration(MIC) and the minimum bactericidal concentration(MBC) of doxycycline against A.hydrophila in extract broth and serum were measured by using the micro-dilution method,in which the final concentration of A.hydrophila was 106 CFU/mL and the incubating temperature was 28 ℃.The pharmacokinetics study of doxycycline was investigated after single oral gavage administration in channel catfish at water temperature of(28±1) ℃.Blood samples were collected at every different intervals before and after ad-ministration,and then made them to be plasma and serum.The concentrations of doxycycline in channel catfish plasma were determined by means of Ultra Performance Liquid Chromatography(UPLC) with UV detection method.The plasma samples were extracted with perchloric acid,then the extracts were centrifuged and the supernatant was sent to UPLC-UV after purified by 0.22 μm filter.5 μL extract was separated on a reversed phase C18 reversion chroma-tographic column(1.7 μm,2.1 mm×50 mm) at 45 ℃,which was then eluted with 0.01 mol/L sodium dihydrogen phos-phate–acetonitrile(4∶1) at a flow of 0.300 mL/min.The UV detection was at λ350nm.Pharmacokinetic parameters were analyzed with the pharmacokinetic computer program 3P97.We learnt the pharmacodynamics effect of doxycycline by detecting the number of A.hydrophila in channel catfish serum sampled at different times.Pharmacodynamics parameters were analyzed with the pharmacodynamic computer program kinetica 4.4.The Pharmacokinetics/pharmacodynamics model parameters were calculated with the MICserum and pharmacokinetic in vivo parameters.The accurate MIC of doxycycline against A.hydrophila in broth and serum were both 2.0 �

关 键 词：强力霉素 嗜水气单胞菌 药动-药效同步模型 斑点叉尾 半体内 

分 类 号：S948[农业科学—水产养殖]