氟苯尼考在健康和弧菌感染梭子蟹体内的药动学比较研究
|
摘要
近年来,随着人工养殖规模和集约化程度的不断扩大和提高,三疣梭子蟹溶藻弧菌病发病率日趋增长、流行范围甚广,严重制约了这一养殖品种的可持续健康发展,急需高效、低毒、低残留的渔用药物对其进行防治。氟苯尼考(Florfenicol,FF)又称氟甲砜霉素,是新一代动物专用的氯霉素类药物,具有广谱抗菌、吸收良好、体内分布广、低毒等特点,目前已被广泛应用于防治各种水产动物细菌性感染疾病。本论文结合当前养殖生产的实际情况筛选了这种具有广阔应用前景的渔用抗菌药物——氟苯尼考,并在建立疾病模型的基础上研究了其在三疣梭子蟹体内的代谢动力学及组织分布,旨在评价氟苯尼考对养殖三疣梭子蟹溶藻弧菌病防治的可行性和安全性,进而为渔药的科学、规范化使用提供理论依据。主要结果如下:
1.氟苯尼考在健康三疣梭子蟹体内的代谢动力学研究
在(21±2)℃水温条件下,按25mg/kg剂量给健康三疣梭子蟹单次口灌氟苯尼考后,采用高效液相色谱法(HPLC)测定了血淋巴和肌肉及肝胰腺组织中的药物浓度。试验结果表明,在设定的色谱条件下,氟苯尼考的色谱行为良好,保留时间为7.815min,在0.05–10μg/mL范围内相关性显著(r=0.9995),最低检测限为0.025μg/mL。氟苯尼考的平均回收率为89.02±6.24%,日内、日间变异系数均在5%以内,说明本方法适用于样品测定。各药时数据表明,氟苯尼考不均匀的广泛分布于三疣梭子蟹全身各组织,其中肝胰腺中药物吸收最快,肌肉较不易吸收和分布。用药7d后健康三疣梭子蟹各组织中的氟苯尼考浓度基本维持在0.1μg/mL以下。3P97药代动力学软件拟合结果表明,氟苯尼考在该三种组织中的代谢过程均符合带时滞的一级吸收二室开放模型,方程分别为C_(血淋巴)= 15.230e~(―0.253t)+0.696e~(-0.015t)-15.926e~(-0.697t),C_(肌肉)= 6.753e~(―0.670t)+1.445e~(-0.014t)-8.198e~(-2.419t),C_(肝胰腺)= 9.222e~(―3.068t)+1.484e~(-0.017t)-10.706e~(-15.886t)。血淋巴、肌肉和肝胰腺中的主要药动学参数如下:达峰时间(T_(peak))分别为2.385h、0.816h和0.143h,消除半衰期(T_(1/2β))分别为46.609h、50.236h和39.903h,达峰浓度(C_(max))分别为5.980μg/mL,4.199μg/mL和6.324μg/mL,清除率(CLs)分别为0.297L/kg·h、0.224L/kg·h和0.285 L/kg·h,表观分布容积(Vd)分别为2.408L/kg、3.957L/kg和2.802L/kg,药时曲线下总面积(AUC)分别为84.153μg/mL·h、111.396μg/mL·h和87.765μg/mL·h,反映该药具有吸收迅速,体内分布广泛,消除缓慢等特点,对三疣梭子蟹的全身感染性疾病防治具有重要的意义。
2.三疣梭子蟹溶藻弧菌病模型的构建
用溶藻弧菌(107CFU/mL)对三疣梭子蟹进行人工感染试验,于感染后0、24、48和72h分别观察蟹体的行动、体表及内部器官组织的病理变化,并测定THCs及血淋巴、肌肉、肝胰腺三种主要组织中的AKP、ACP、POD活性和T–AOC水平。结果表明:三疣梭子蟹感染溶藻弧菌24h后其行动、体表及内部器官组织等病理症状逐渐明显,肝胰腺、血淋巴、肌肉等三种主要组织中的AKP、ACP、POD活性和T–AOC水平及THCs均发生了显著变化。由于药物防治的主要对象为早期发病群体,因此本研究中以感染病原菌24h后蟹体内的THCs、AKP、ACP、POD和T–AOC等指标作为其疾病模型是否构建成功的的判断依据,且采用上述方法构建的三疣梭子蟹溶藻弧菌病模型在相同条件下可重复性较强,并便于观测感染前后蟹体的变化情况。
3.疾病模型下氟苯尼考在三疣梭子蟹体内的代谢动力学研究
在(21±2)℃水温条件下,疾病模型下以25mg/kg剂量的氟苯尼考对三疣梭子蟹口灌给药后,其血淋巴、肌肉和肝胰腺中的药物代谢过程均符合带时滞的一级吸收二室开放模型,方程分别为C血淋巴= 18.071e―0.249t+1.711e-0.012t-19.782e-0.3933t,C肌肉= 19.012e―0.676t+1.440e-0.011t-20.452e-0.874t,C肝胰腺= 19.283e―3.286t+1.427e-0.014t-20.710e-4.363t。血淋巴、肌肉和肝胰腺中的主要药动学参数如下:达峰时间(Tpeak)分别为3.700h、1.662h和0.331 h,消除半衰期(T1/2β)分别为55.667 h、63.349h和48.437h,达峰浓度(Cmax)分别为4.209μg/mL,2.809μg/mL和3.032μg/mL,清除率(CLs)分别为0.157L/kg·h、0.183L/kg·h和0.248 L/kg·h,表观分布容积(Vd)分别为3.017L/kg、4.366L/kg和4.043L/kg ,药时曲线下总面积(AUC)分别为159.649μg/mL·h、136.329μg/mL·h和100.843μg/mL·h。与健康组相比,溶藻弧菌感染可以改变三疣梭子蟹血淋巴、肌肉和肝胰腺中的药动学参数,使其吸收和消除速度减慢、达峰时间推迟、半衰期延长、清除率减低、最高药物浓度下降、表观分布容积和药时曲线下总面积变大。假设口服给药的生物利用度为100%,建议以25 mg/kg剂量口灌给药时,采用首剂加倍,每日给药2次,给药时间间隔为12h的给药方案。若以农业部《动物性食品中兽药最高残留限量》规定的氟苯尼考最高残留限量0.1mg/kg为标准,建议患病三疣梭子蟹口服氟苯尼考的休药期不低于250度日,即水温为25℃时,休药期应≥10d。
With the development of the intensive aquaculture system model , the incidence and severity of Vibrio alginolyticus disease of Portunus trituberculatus are on the rise. This is a restrict factor for sustainable development,so some high-effective and low-poisonous and less-residual antimicrobial substance must be investigated for Portunus trituberculatus. Florfenicol, also called the fluorine Thiamphenicol, is a kind of chloramphenicols exclusively used in veterinary medicine, which has wide antibacterial spectrum and low toxicity and was completely absorbed and distributed. It has been widely intended for the treatment of infectious diseases in some aquatic animals.
In this study, the pharmacokinetics and tissue distribution of florfenicol in the Vibrio alginolyticus diseased Portunus trituberculatus were investigated firstly, so as to appraise its feasibility and security,to provide the scientific basis for the standardization application of fishery drugs in aquaculture. The main results are:
1. Pharmacokinetics of florfenicol in healthy Portunus trituberculatus
The concentrations of florfenicol were determined in haemolymph, muscle, hepatopancreas of Portunus trituberculatus following oral administration in a single dose of 25 mg/kg at (21±2)℃by using high performance liquid chromatography (HPLC).The results showed that the retention rime for florfenicol was 7.815min with no interference from endogenous components. The calibration curve exhibited excellent linearity over a rang of 0.05–10μg/mL(r=0.9995). The limit of detection(LOD) was 0.025μg/mL .The average recovery was 89.02±6.24% and the RSDs of intra-day and inter-day were all less than 5%. So the validated HPLC method was suitable for the measurement of florfenicol concentration. Florfenicol can unevenly distributed to all tissues, absorbed most quickly by hepatopancreas. Their concentration of florfenicol were all lower than 0.1μg/mL after oral administration for 7 days. The concentration-time data of haemolymph, muscle, hepatopancreas were all described by two-compartment open model with first-order absorb, described with C= 15.230e~(―0.253t)+0.696e~(-0.015t)-15.926e~(-0.697t),C= 6.753e~(―0.670t)+1.445e~(-0.014t)-8.198e~(-2.419t) , C= 9.222e~(―3.068t) + 1.484e ~(- 0.017t) - 10.706e ~(-15.886t), respectively. The main pharmacokinetic parameters were as follows: Haemolymph: T_(peak)=2.385h,T_(1/2β)=46.609h,C_(max) =5.980μg/mL,CLs=0.297L/kg·h,Vd=2.408L/kg,AUC=84.153μg/mL·h;Muscle:T_(peak)=0.816h,T_(1/2β)=50.236h,C_(max)=4.199μg/mL,CLs=0.224L/kg·h,Vd=3.957L/kg,AUC=111.396μg/mL·h;Hepatopancreas:T_(peak)=0.143h,T_(1/2β)=39.903h,C_(max)=6.324μg/mL,CLs=0.285L/kg·h,Vd=2.802L/kg, AUC=87.765μg/mL·h.So florfenicol could be absorbed quickly , distributed widely and eliminated slowly,which had an efficient effect of antibacterial in Portunus trituberculatus.
2. Establishment of a Vibrio alginolyticus disease model for Portunus trituberculatus
Portunus trituberculatus was infected artificially with Vibrio alginolyticus with a concentration of 107CFU/mL. The external symptoms and histopathological changes of infected crab were observed and the physio-biochemical indexes were determined at 0, 24, 48 and 72h post-injection. The results indicated that the pathological changes of the infected crab were obvious gradually at 24h post-injection and THCs、T-AOC、AKP、ACP and POD had significant changes. The main objection of drug prevention was early diseased population, so the indexes, such as THCs、T-AOC、AKP、ACP and POD, in the crab which was infected 24 hours can be used to determine whether the establishment of disease model was successful in this paper. The Vibrio alginolyticus disease model for Portunus trituberculatus which was established by this method was reproducible highly and convenient for observing changes of crabs.
3. Pharmacokinetics of florfenicol in Vibrio alginolyticus diseased Portunus trituberculatus
The pharmacokinetic characteristics of haemolymph, muscle, hepatopancreas of Vibrio alginolyticus diseased Portunus trituberculatus in a single dose of 25mg/kg at (21±2)℃were all fitted with by two-compartment open model with first-order absorb, described with C = 18.071e―0.249t+1.711e-0.012t-19.782e-0.3933t,C= 19.012e―0.676t+1.440e-0.011t-20.452e-0.874t,C= 19.283e―3.286t + 1.427e -0.014t - 20.710e -4.363t, respectively. The main pharmacokinetic parameters were as follows: Haemolymph: Tpeak=3.700h,T1/2β=55.667h,Cmax=4.209μg/mL, CLs= 0.157L/kg·h, Vd=3.017L/kg, AUC=159.649μg/mL·h; Muscle: Tpeak=1.662h, T1/2β=63.349h,Cmax= 2.809μg/mL,CLs=0.248L/kg·h,Vd=4.366L/kg,AUC=136.329μg/mL·h;Hepatopancreas:Tpeak=0.331h,T1/2β=48.437h,Cmax=3.032μg/mL,CLs=0.183L/kg·h,Vd=4.043L/kg,AUC=100.843μg/mL·h.Campared with the healthy Portunus trituberculatus, the pharmacokinetic parameters of florfenicol in infected Portunus trituberculatus had great changes. The rate of absorption and elimination slowed, Tpeak and t1/2βprolonged, Cmax and CLs decreased,Vd and AUC increased. Supposed that the bioavailability was 100%,we suggested that the dose of clinical should be 50mg/kg for the first time and the maintenance dose should be 25mg/kg per 12hours. According to the maximum residue limit (MRL) of 0.1mg/kg in tissues,the withdrawal period should not be less than 10daysunder this experiment condition.
1.氟苯尼考在健康三疣梭子蟹体内的代谢动力学研究
在(21±2)℃水温条件下,按25mg/kg剂量给健康三疣梭子蟹单次口灌氟苯尼考后,采用高效液相色谱法(HPLC)测定了血淋巴和肌肉及肝胰腺组织中的药物浓度。试验结果表明,在设定的色谱条件下,氟苯尼考的色谱行为良好,保留时间为7.815min,在0.05–10μg/mL范围内相关性显著(r=0.9995),最低检测限为0.025μg/mL。氟苯尼考的平均回收率为89.02±6.24%,日内、日间变异系数均在5%以内,说明本方法适用于样品测定。各药时数据表明,氟苯尼考不均匀的广泛分布于三疣梭子蟹全身各组织,其中肝胰腺中药物吸收最快,肌肉较不易吸收和分布。用药7d后健康三疣梭子蟹各组织中的氟苯尼考浓度基本维持在0.1μg/mL以下。3P97药代动力学软件拟合结果表明,氟苯尼考在该三种组织中的代谢过程均符合带时滞的一级吸收二室开放模型,方程分别为C_(血淋巴)= 15.230e~(―0.253t)+0.696e~(-0.015t)-15.926e~(-0.697t),C_(肌肉)= 6.753e~(―0.670t)+1.445e~(-0.014t)-8.198e~(-2.419t),C_(肝胰腺)= 9.222e~(―3.068t)+1.484e~(-0.017t)-10.706e~(-15.886t)。血淋巴、肌肉和肝胰腺中的主要药动学参数如下:达峰时间(T_(peak))分别为2.385h、0.816h和0.143h,消除半衰期(T_(1/2β))分别为46.609h、50.236h和39.903h,达峰浓度(C_(max))分别为5.980μg/mL,4.199μg/mL和6.324μg/mL,清除率(CLs)分别为0.297L/kg·h、0.224L/kg·h和0.285 L/kg·h,表观分布容积(Vd)分别为2.408L/kg、3.957L/kg和2.802L/kg,药时曲线下总面积(AUC)分别为84.153μg/mL·h、111.396μg/mL·h和87.765μg/mL·h,反映该药具有吸收迅速,体内分布广泛,消除缓慢等特点,对三疣梭子蟹的全身感染性疾病防治具有重要的意义。
2.三疣梭子蟹溶藻弧菌病模型的构建
用溶藻弧菌(107CFU/mL)对三疣梭子蟹进行人工感染试验,于感染后0、24、48和72h分别观察蟹体的行动、体表及内部器官组织的病理变化,并测定THCs及血淋巴、肌肉、肝胰腺三种主要组织中的AKP、ACP、POD活性和T–AOC水平。结果表明:三疣梭子蟹感染溶藻弧菌24h后其行动、体表及内部器官组织等病理症状逐渐明显,肝胰腺、血淋巴、肌肉等三种主要组织中的AKP、ACP、POD活性和T–AOC水平及THCs均发生了显著变化。由于药物防治的主要对象为早期发病群体,因此本研究中以感染病原菌24h后蟹体内的THCs、AKP、ACP、POD和T–AOC等指标作为其疾病模型是否构建成功的的判断依据,且采用上述方法构建的三疣梭子蟹溶藻弧菌病模型在相同条件下可重复性较强,并便于观测感染前后蟹体的变化情况。
3.疾病模型下氟苯尼考在三疣梭子蟹体内的代谢动力学研究
在(21±2)℃水温条件下,疾病模型下以25mg/kg剂量的氟苯尼考对三疣梭子蟹口灌给药后,其血淋巴、肌肉和肝胰腺中的药物代谢过程均符合带时滞的一级吸收二室开放模型,方程分别为C血淋巴= 18.071e―0.249t+1.711e-0.012t-19.782e-0.3933t,C肌肉= 19.012e―0.676t+1.440e-0.011t-20.452e-0.874t,C肝胰腺= 19.283e―3.286t+1.427e-0.014t-20.710e-4.363t。血淋巴、肌肉和肝胰腺中的主要药动学参数如下:达峰时间(Tpeak)分别为3.700h、1.662h和0.331 h,消除半衰期(T1/2β)分别为55.667 h、63.349h和48.437h,达峰浓度(Cmax)分别为4.209μg/mL,2.809μg/mL和3.032μg/mL,清除率(CLs)分别为0.157L/kg·h、0.183L/kg·h和0.248 L/kg·h,表观分布容积(Vd)分别为3.017L/kg、4.366L/kg和4.043L/kg ,药时曲线下总面积(AUC)分别为159.649μg/mL·h、136.329μg/mL·h和100.843μg/mL·h。与健康组相比,溶藻弧菌感染可以改变三疣梭子蟹血淋巴、肌肉和肝胰腺中的药动学参数,使其吸收和消除速度减慢、达峰时间推迟、半衰期延长、清除率减低、最高药物浓度下降、表观分布容积和药时曲线下总面积变大。假设口服给药的生物利用度为100%,建议以25 mg/kg剂量口灌给药时,采用首剂加倍,每日给药2次,给药时间间隔为12h的给药方案。若以农业部《动物性食品中兽药最高残留限量》规定的氟苯尼考最高残留限量0.1mg/kg为标准,建议患病三疣梭子蟹口服氟苯尼考的休药期不低于250度日,即水温为25℃时,休药期应≥10d。
With the development of the intensive aquaculture system model , the incidence and severity of Vibrio alginolyticus disease of Portunus trituberculatus are on the rise. This is a restrict factor for sustainable development,so some high-effective and low-poisonous and less-residual antimicrobial substance must be investigated for Portunus trituberculatus. Florfenicol, also called the fluorine Thiamphenicol, is a kind of chloramphenicols exclusively used in veterinary medicine, which has wide antibacterial spectrum and low toxicity and was completely absorbed and distributed. It has been widely intended for the treatment of infectious diseases in some aquatic animals.
In this study, the pharmacokinetics and tissue distribution of florfenicol in the Vibrio alginolyticus diseased Portunus trituberculatus were investigated firstly, so as to appraise its feasibility and security,to provide the scientific basis for the standardization application of fishery drugs in aquaculture. The main results are:
1. Pharmacokinetics of florfenicol in healthy Portunus trituberculatus
The concentrations of florfenicol were determined in haemolymph, muscle, hepatopancreas of Portunus trituberculatus following oral administration in a single dose of 25 mg/kg at (21±2)℃by using high performance liquid chromatography (HPLC).The results showed that the retention rime for florfenicol was 7.815min with no interference from endogenous components. The calibration curve exhibited excellent linearity over a rang of 0.05–10μg/mL(r=0.9995). The limit of detection(LOD) was 0.025μg/mL .The average recovery was 89.02±6.24% and the RSDs of intra-day and inter-day were all less than 5%. So the validated HPLC method was suitable for the measurement of florfenicol concentration. Florfenicol can unevenly distributed to all tissues, absorbed most quickly by hepatopancreas. Their concentration of florfenicol were all lower than 0.1μg/mL after oral administration for 7 days. The concentration-time data of haemolymph, muscle, hepatopancreas were all described by two-compartment open model with first-order absorb, described with C= 15.230e~(―0.253t)+0.696e~(-0.015t)-15.926e~(-0.697t),C= 6.753e~(―0.670t)+1.445e~(-0.014t)-8.198e~(-2.419t) , C= 9.222e~(―3.068t) + 1.484e ~(- 0.017t) - 10.706e ~(-15.886t), respectively. The main pharmacokinetic parameters were as follows: Haemolymph: T_(peak)=2.385h,T_(1/2β)=46.609h,C_(max) =5.980μg/mL,CLs=0.297L/kg·h,Vd=2.408L/kg,AUC=84.153μg/mL·h;Muscle:T_(peak)=0.816h,T_(1/2β)=50.236h,C_(max)=4.199μg/mL,CLs=0.224L/kg·h,Vd=3.957L/kg,AUC=111.396μg/mL·h;Hepatopancreas:T_(peak)=0.143h,T_(1/2β)=39.903h,C_(max)=6.324μg/mL,CLs=0.285L/kg·h,Vd=2.802L/kg, AUC=87.765μg/mL·h.So florfenicol could be absorbed quickly , distributed widely and eliminated slowly,which had an efficient effect of antibacterial in Portunus trituberculatus.
2. Establishment of a Vibrio alginolyticus disease model for Portunus trituberculatus
Portunus trituberculatus was infected artificially with Vibrio alginolyticus with a concentration of 107CFU/mL. The external symptoms and histopathological changes of infected crab were observed and the physio-biochemical indexes were determined at 0, 24, 48 and 72h post-injection. The results indicated that the pathological changes of the infected crab were obvious gradually at 24h post-injection and THCs、T-AOC、AKP、ACP and POD had significant changes. The main objection of drug prevention was early diseased population, so the indexes, such as THCs、T-AOC、AKP、ACP and POD, in the crab which was infected 24 hours can be used to determine whether the establishment of disease model was successful in this paper. The Vibrio alginolyticus disease model for Portunus trituberculatus which was established by this method was reproducible highly and convenient for observing changes of crabs.
3. Pharmacokinetics of florfenicol in Vibrio alginolyticus diseased Portunus trituberculatus
The pharmacokinetic characteristics of haemolymph, muscle, hepatopancreas of Vibrio alginolyticus diseased Portunus trituberculatus in a single dose of 25mg/kg at (21±2)℃were all fitted with by two-compartment open model with first-order absorb, described with C = 18.071e―0.249t+1.711e-0.012t-19.782e-0.3933t,C= 19.012e―0.676t+1.440e-0.011t-20.452e-0.874t,C= 19.283e―3.286t + 1.427e -0.014t - 20.710e -4.363t, respectively. The main pharmacokinetic parameters were as follows: Haemolymph: Tpeak=3.700h,T1/2β=55.667h,Cmax=4.209μg/mL, CLs= 0.157L/kg·h, Vd=3.017L/kg, AUC=159.649μg/mL·h; Muscle: Tpeak=1.662h, T1/2β=63.349h,Cmax= 2.809μg/mL,CLs=0.248L/kg·h,Vd=4.366L/kg,AUC=136.329μg/mL·h;Hepatopancreas:Tpeak=0.331h,T1/2β=48.437h,Cmax=3.032μg/mL,CLs=0.183L/kg·h,Vd=4.043L/kg,AUC=100.843μg/mL·h.Campared with the healthy Portunus trituberculatus, the pharmacokinetic parameters of florfenicol in infected Portunus trituberculatus had great changes. The rate of absorption and elimination slowed, Tpeak and t1/2βprolonged, Cmax and CLs decreased,Vd and AUC increased. Supposed that the bioavailability was 100%,we suggested that the dose of clinical should be 50mg/kg for the first time and the maintenance dose should be 25mg/kg per 12hours. According to the maximum residue limit (MRL) of 0.1mg/kg in tissues,the withdrawal period should not be less than 10daysunder this experiment condition.
引文
艾晓辉,陈正望.磺胺二甲嘧啶在银鲫体内的药动学及组织残留研究[J].淡水渔业,2001,31(6):52–54.
蔡雪峰,罗琳,李素珍,等.日本沼虾血细胞的初步研究[J].水生生物学报,2000,24(3):289–292.
陈眷华,彭羽.氯霉素类抗生素药物对人类健康的威胁[J].贵州畜牧兽医,2006,30(4):17–18.
陈四清.饲喂土霉素对鲤鱼生长及代谢残留的研究[J].饲料工业,1997,18(5):19–20.
陈文银,印春华.诺氟沙星在中华鳖体内的药代动力学研究[J].水产学报,1997,21(4):434–437.
陈晓慧,刘阳春,焦阳.氟苯尼考的研究新进展及其应用[J].现代畜牧兽医,2006,51(4):51-54.《动物性食品中兽药最高残留限量》,中华人民共和国农业部公告第235号.
杜向党,阎若潜,沈建忠.氯霉素类药物耐药机制的研究进展[J].动物医学展,2004,25(2):27-29.
樊甄姣,杨爱国,吕振明,等.鳗弧菌注射对栉孔扇贝免疫活性的影响[J].南方水产,2007,3(6):52-55.
方星星,李健,王群,等.复方新诺明在花鲈体内的残留及消除规律[J].海洋科学,2003,(9):18-20.
房文红.斑节对虾血淋巴中诺氟沙星含量测定及药代动力学[J].水生生物学报,2003,27(1):13-17.
冯敬宾,李刘冬,贾晓平.氟苯尼考在罗非鱼体内的药物动力学[J].南方水产,2006,2(5):25-29.
冯守明,杨先乐,李军,等.凡纳滨对虾白斑综合征血液病理研究[J].水产学报,2006,30(1):108-112.
郭闯,朱国强,王永坤,等.14株患病水生动物气单胞菌属细菌的分离鉴定与最佳治疗药筛选试验[J].水产科学,2003,22(4):14-17.
洪振涛.气相色谱法测定动物组织中氯霉素的残留量[J].中国兽药杂志,2006,40(2):14-16.
胡顶飞,沈建忠,吴先爱,等.氟苯尼考静注及肌注在鸡体内药代动力学研究[J].畜牧兽医学报,2002,33(4):384-388.
胡功政,苑丽,刘智明,等.氟苯尼考及其与多西环素联合的体外抗菌作用[J].中国兽医学报,2004,24(4):379-383.
黄显会,陈杖榴,张淑婷,等.禽多杀性巴氏杆菌感染对麻保沙星在鸡体内药动学特征的影响研究[J].畜牧兽医学报,2003,34(1):98-102.
黄志坚,何建国.鲑点石斑鱼细菌病原的分离鉴定和致病性[J].中山大学学报(自然科学版),2002,41(5):64-67.
金珊,蔡完其,王国良,等.养殖大黄鱼细菌性疾病的病原研究[J].浙江海洋学院学报(自然科学版),2002,21(3):225-230.
李爱华.氯霉素在草鱼和复合四倍体异育银鲫体内的比较药代动力学[J].中国兽医报,1998,18(4):372-374.
李建勇,赵荣材.我国兽医药物代谢动力学研究进展[J].中国兽药杂志,1999,33(4):44- 47.
李健,王群,孙修涛,等.噁喹酸对水生生物细菌病的防治效果及残留研究[J].中国水产学,2001,(3):45-49.
李静云,李健,王群,等.氟苯尼考3种不同给药方式在中国明对虾体内的药代动力学研究[J].海洋科学,2006,30(7):64-68.
李静云,李健,王群,等.磺胺间甲氧嘧啶在中国对虾体内的药代动力学研究[J].海洋水产研究,2006,27(4):6-11.
李静云,王群,李健,等.氟苯尼考在中国对虾组织内的代谢动力学及残留消除规律[J].水产学报,2004,28:63-68.
李兰生,王勇强.氯霉素在对虾体内的动力学研究[J].色谱,1997,15(5):431-434.
李美同,郭文林,郑国兴,等.土霉素在鳗鲡组织中残留的消除规律[J].水产学报,1997,21(1):39-43.
李秀波,沈建忠,胡顶飞,等.氟苯尼考静注及肌注在绵羊体内的药代动力学研究[J].畜牧兽医学报,2003,34(6):609-612.
李秀波,石波,梁萍.新型广谱抗菌药――氟苯尼考[J].国外畜牧科技,1999,(3):50-52.
李正,杨勇,杨先乐,等.盐酸环丙沙星药液口灌在中华绒螯蟹体内的代谢动力学研究[J].水产学报,2004,28 (增):25-29.
李佐卿,倪梅林,章再婷,等.高效液相色谱法检测水产品中喹诺酮类药物残留[J].现代科学仪器,2006,(3):70-71.
梁文权.生物药剂学与药物动力学[M].北京:人民卫生出版社,2004.
梁增辉,林黎明,刘靖靖,等.噁喹酸和氟甲喹在鳗鱼体内的药代动力学研究[J].海洋水产研究,2006,27(3):86-92.
廖昌容,徐力文,陈毕生,等.氟苯尼考对六种海洋致病弧菌的体外抗菌活性研究[J].水产养殖,2005,26(4):1-4.
刘涤洁,冯淇辉,陈杖榴,等.恩诺沙星在健康及实验性感染乳房炎奶山羊间的比较药动学[J].中国农业科学,2003,36(9):1100-1104.
刘彦,李健,王群,等.达氟沙星在健康和鳗弧菌感染牙鲆体内的药物代谢动力学比较[J].水产学报,2006,30(4):509-514.
刘彦,李健,王群,等.鳗弧菌感染牙鲆药物代谢动力学模型的初步建立[J].海洋水产研究,2007,28(2):76-83.
刘永涛,艾晓辉,杨红.不同水温下氟甲砜霉素在斑点叉尾鮰体内的药代动力学研究[J].水生生物学报,2009,(1):1-6.
刘玉林,王翔凌,杨先乐,等.诺氟沙星在大黄鱼体内的药代动力学及残留研究[J].水产学报,2007,31(5):655–660.
刘元元.药物动力学及药物动力学的新进展[J].河北农业科技,2008,12(9):168-170.
骆永泉,邓绍基.氟苯尼考防治猪传染性胸膜肺炎与链球菌病效果观察[J].养猪,2004,(2):53.
毛芝娟,卓华龙.锯缘青蟹细菌性传染病的病原菌研究[J].水产科学,2001,20(1):8-11.
孟勇,吴光红,朱晓华,等.RP-HPLC同时测定中华绒螯蟹肝脏中诺氟沙星、环丙沙星和恩诺沙星残留[J].中国水产科学,2005,(6):772-778.
农业部《新编渔药手册》编撰委员会.新编渔药手册[M].中国农业出版社,2005:318. NY5071-2002.中华人民共和国农业部,无公害食品渔用药物使用准则[S].
帕它木,黄贤仪,龚建福.氧化锂对小鼠脂质过氧化及抗氧化酶的影响[J].劳动医学(Labour Med),2000,17(1):25-26.
区炳庆,刘富来,潘燕琼,等.肠炎沙门氏杆菌感染雏鸭脾脏过氧化氢酶及过氧化物酶活性的变化[J].黑龙江畜牧兽医,2005,(3):11-13.
曲晓荣,王印庚,李胜忠,等.诺氟沙星在大菱鲆体内药代动力学及残留消除规律[J].海洋水产研究,2007,28(5):24-29.
苏成业.临床药物代谢动力学[M].北京:科学出版社,2003.
孙虎山,李光友.大肠杆菌感染后栉孔扇贝血淋巴中7种酶活力的变化[J].海洋科学,1999,(5):39-44.
谭志军,翟毓秀,冷凯良,等.呋喃西林和呋喃唑酮代谢物在大菱鲆组织中的消除规律[J].中山大学学报(自然科学版),2008,47(增刊):63-69.
唐俊,郑宗林,杨先乐,等.磺胺甲基异噁唑在中华绒螯蟹体内的代谢和消除规律[J].上海水产大学学报,2006,(4):449-455.
唐雪莲,佟恒敏.喹诺酮类药物研究进展及在兽医临床的应用问题[J].黑龙江畜牧兽医,2001,(3): 24-26.
唐雪莲,王群,李健.氯霉素在鲈鱼体内的药代动力学及残留的研究[J].海洋水产研究, 2003,24(2):45-50.
王国良,金珊,陈寅儿,等.三疣梭子蟹肌肉乳化病的病原及其致病性研究[J].海洋科学进展, 2006,24(4):526-531.
王国良,金珊,李政,等.三疣梭子蟹(Portunus trituberculatus)乳化病的组织病理和超微病理研究[J].海洋与湖沼,2006,37(4):297-303.
王丽平,陈绍峰,史晓丽,等.复方氟苯尼考口服液对人工诱发鸡大肠杆菌病的疗效试验[J].动物医学进展,2003,24(4):110-112.
王群.成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.
王群.氟苯尼考在中国对虾体内消除规律的研究[J].水产学报, 2004, 28(增):63-68.
王淑红,王艺磊,张朝霞,等.弧菌和大肠杆菌感染对杂色鲍无细胞血淋巴中几种酶活力的影响[J].中国水产科学,2004,11(1):37-40.
王武.我国水产养殖业的现状与发展趋势[J].渔业致富指南,2009,(7):12-17.
王志杰,冷凯良,孙伟红,等.水产品中氯霉素、甲砜霉素和氟甲砜霉素残留量高效液相色谱-串联质谱内标测定方法的研究[J].渔业科学进展,2009,(2):115-119.
王自然,朱文峰.氟苯尼考对耐氯霉素大肠杆菌菌株的体外药敏试验[J].中国家禽,2003,25(18):17.
谢剑华,管越强,王静波.虾青素对日本沼虾血细胞密度及吞噬活力的影响[J].河北渔业,2008,(1):8-13.
徐力文,廖昌容,王瑞旋,等.氟苯尼考在九孔鲍体内的药代动力学初步研究[J].台湾海峡, 2006,2:217-221.
杨成对,宋莉晖.对虾中氯霉素残留的分析方法研究[J].分析化学研究简报,2004,32(7):905-907.
杨先乐,刘至致,横山雅仁.盐酸环丙沙星在中华绒螯蟹体内的药物代谢动力学[J].水生生物学报,2003,27(1):18-22.
杨先乐,湛嘉,胡鲲.氯霉素在尼罗罗非鱼血浆中的药代动力学研究[J].水产学报, 2005,29(1):60-65.
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.
杨先乐,朱丽敏,林启存,等.肌注和口服氟苯尼考在中华鳖体内残留分析及药代动力学[J].水产学报,2006,30(4):515-519.
杨贤庆,李来好,郝淑贤,等.土霉素在凡纳滨对虾肌肉组织中残留情况的研究[J].热带海洋学报,2007,26(3):53-56.
叶雪珠,王小骊,赵燕申,等.水产品中氯霉素含量的快速检测与分析[J].食品科技,2003,(8):83-85.
叶燕玲,陈宽智.中国对虾(Penaeus chinesis)血细胞超微结构、分类及计数[J].青岛海洋大学学报,1993,23(2):35-42.
于占国,林风翱,卞正和,等.溶藻弧菌引起中国对虾红腿病的回接实验观察[J].海洋学报(中文版),1996,18(6):135-139.
余培建,翁祖桐,樊海平,等.氟苯尼考在欧洲鳗鲡体内的药物代谢动力学的研究[J].福建水产,2005,(4):54-57.
袁宗辉,廖小群,尹烨华,等.药物代谢动力学猪链球菌病模型的研制[J].畜牧兽医学报,1994,25(5):430-435.
战文斌,刘洪明,王越.水产养殖病害及其药物控制与水产品安全[J].中国海洋大学学报,2004,34(5):758-760.
张春玲,胡俊峰,王丕文,等.苯并(a)芘对鲫鱼肝脏总抗氧化能力的影响[J].环境与健康杂志,2004,21(5):325-326.
张培旗,李健,王群,等.磺胺甲基异噁唑在中国明对虾体内的残留和消除规律[J].水产科学,2005,24(11):17-20.
张收元,操继跃,罗宇良.氟苯尼考在鲫体内的药动学研究[J].水利渔业,2007,27(3):97-99.
张秀英,佟恒敏,姚春翥,等.单诺沙星在健康与支原体-大肠杆菌合并感染鸡体内的药动学研究[J].畜牧与兽医,2002,34(2):5-8.
张秀英.单诺沙星在健康和支原体-大肠杆菌感染鸡的药动学与药效学研究[D].东北农业大学, 2001.
张雅斌.不同给药方式下鲤鱼对诺氟沙星的药代动力学研究[J].水产学报,2000,24(6):559 -563.
张祚新,张雅斌,杨永胜,等.诺氟沙星在鲤鱼体内的药代动力学[J].中国兽医学报,2000,20(1):66-69.
郑宗林,刘鸿艳,黄辉,等.复方新诺明在罗氏沼虾中的药代动力学和组织分布[J].广东海洋大学学报,2008,28(4):54-59.
中华人民共和国药典委员会.中华人民共和国药典2000年版二部[S].北京:中国农业出版社:711-712.
朱秋华,钱国英.3种药物在甲鱼体内的残留研究[J].中国水产科学,2001,8(3):50-53.
朱忠勇.实用医学检验学[M].北京:人民军医出版社,1997:368-378.
Abedini S, Namdari R, Law F C P. Comparative pharmacokinetics and bicavailability of oxytetr-acycline in rainbow trout and chinook salmon following in traarterial administration[J]. Aquaculture,1998,162:23-32.
Baggot J D. Distribution of antimicrobial agents in normal and diseased animals[J]. J Am Vet Med Assoc,1980,176(10):1085-1090.
Bernt M, Tor E H, Kanval J V, et al..Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11℃[ J]. Aquaculture,1993,112:1-11.
Bjorklund H V. Temperature-ralated absorption and excretion of oxolinic acid in rainbow trout (Oncorhynchus mykiss)[J]. Aquaculture,1992,102(1):17-27.
BreganteM A, Abadia A R, Aramayoma J J, et al.. Phamacokinetics of enrofloxacin in rainbow trout after a single intravascular injection[J]. Actas Deliv Congreso Nactional de Acuicultura, Centrode Investigaciones Marinas, Pontevedr (Spain),1993,709-712.
Carignan G, Carrier K, Sved S. Assay of Oxytetracycline residues in salmon muscle by liquid chr-omatography with ultraviolet detection[J]. JAOACInt.,1993,76(2):325-328.
Carignan G.Assay of Oxolinic Acid Resudues in Salmon Muscle by Liquid Chromatography with Fluorescence Detection:Interlaboratory Study[J]. Journal of AOAC iternational,1991,74 (6):906-909.
Chue V, Larry J S,Guy R, et al.. Liquid chromatographic determination of florfenicol in the pla-sma of multiple species of fish[J]. Journal of Chromatography B,2002,780(1):111-117.
Cravedi J P. Digestibility of clorampheicol, oxolinic acid and oxytetracycline in rainbow trout and influence of these antibiotics on lipid digestibility[J]. Aquaculture,1987,60:133-141.
Damrongsak F, Ausa C, Sommai C, et al..Bioavailability and absorption analysis of oxytetracycl-ine orally administered to the standardized moulting farmed Pacific white shrimps (Penaeus vannamei)[J]. Aquaculture,2007,(269):89–97.
Dario L,Laura F,Emilio G,et al.. Long depletion time of enrofloxacin in rainbow trout (Oncorhync-hus mykiss)[J]. Antimicrobial Agents and Chemot herapy,2004,48(10):3912-3917.
Elema M O. Bioavailability of oxtetrycline from medicated feed administered to atlantic salmon (Salmo salar L .) in seawater[J]. Aquaculture,1996,143:7-14.
FAO 2002. Antibiotic residues in aquaculture products, The State of World Fisheries andAquaculture 2002.
Feng T, Zheng W, Hong W,et al.. Effect of benzo(a)pyrene on antioxidant enzyme activities in Boleophthalmus pectinirostris live[J]. Ying Yong Sheng Tai Xue Bao,2001,12:422-424.
Fukui H, Fujihara Y, Kano Y. Invitro and in vivo antibacterial activities of florfennicol, a new fluorinated analog of thiamphenicol, against fish pathogens[J]. FishPathol,1987,22:201?207.
Gentleman M S. High-performance liquid chromatographic determination of sulphadiazine and trimethoprim in chinook salmon muscle tissue[J]. Journal of Chromatography,1993, 633.
George R, Ioannis N, Athanassios E T, et al.. Pharmacokinetics and bioavailability of oxytetracyc- line in gilthead sea bream (Sparus aurata) after a single dose[J].Aquaculture,2003,(221):75–83.
George R, Ioannis N, Maria A. Tissue distribution and residue depletion of oxolinic acid in gilthead sea bream (Sparus aurata) and sharpsnout sea bream (Diplodus puntazzo) following multiple in-feed dosing[J]. Aquaculture,2003,(224):245?256.
Grondel J L, Nouws J F M. Pharmacokinetics and tissue distribution of oxy- tetracycline in carp, cyprinus carpip L, follows different routes of administration[J]. Journal of Fish Disease,1987,10(3):153-163.
Heaton L H. Tissue Residue and Oral Safety of Fuurazolidone in Four Species of Trout [J]. Progr Fish-Culturist,1968,30:208-215.
Heijden H J. Plasma disposition of flumequine in common carp, African catfish and European eel after a single peroral administration[J]. Aquaculture, 1994, 123:21-30.
Herman R L, Degurse P E. Sulfamerazine residues in trout tissues[J]. Ichthyologica,1967,39:73-79.
Ho S P, Cheng C F, Wang W S. Pharmacokinetic and depletion studies of sarafloxac in after oral adminstration to eel (Anguilla anguilla)[J]. Journal of Veterinary Medical Science,1999,61 (5):459 -463.
Ho S P, Hsu T Y, Chen M H, et al.. Antibacterial effect of chloramphenicol, thiamphenicol and florfenicol against aquatic animal bacteria[J]. The Journal of Veterinary Medical Science, 2000,62:479-485.
Hormazabal V, Steffenak I, Yndestad M. Simutaneous extraction and determinition of residues of florfenicol and the metabolite florfenicol amine in fish tissues by high-performance liquid chromatography[J]. J Chromatogr,1993,616:161-165.
Horsberg T E, Hoff K A, Nordmo R. Pharmacokinetic of florfenicol and its metabolite florfenicol amine in Atlantic salmon[J]. Journal of Aquatic Animal Health,1996,8:292-301.
Horsberg T E, Martinsen B, Varma K J. The disposition of 14C-florfenicol in Atlantic salmon (Salmo salar)[J]. Aquaculture,1994,122:97?106.
Iwata K, Tanohara Y, Ishibashi O. Studies on factors related to mortality of young red seabream (Pagrus major)in the artfical seed production[J]. Fish pathology,1978,13:97-102.
Intorre L, Cecchini S, Bertini S, et al.. Pharmacokinetics of enrofloxacin in the seabass (Dicentrar-chus labrax)[J]. Aquaculture,2000,(182):49–59.
Lackie A M. Invertebrate immunity [J]. Parasitology,1980,80:393-412.
Lee K K. Pathogenesis studies on Vibrio alginolyticus in th grouper, Epinephelus malabaricus Bloch et Schneider [J]. Microbial Pathogenesis,1995,19:39-48.
Martinsen B. Single dose kinetic Study of sarafloxacin after intravenous and oral administra -tion of different formulations to Atlantic salmon (Salmo salar) held in sea water at 8.5 degree C[J]. Aquaculture,1993(118):37-47.
Martinsen B, Horsberg T E, Varma K J, et al.. Single dose pharmacokinetic study of florfenicol in Atlantic salmon in seawater at 11℃[J]. Aquaculture,1993,112:1-11.
Michel C M F. Pharmacokinetics and metabolism of sulfadimethoxine in channel catfish (Ictalurus punctatus)[J]. Dissertation abstracts international part B:science and engineering,1990,51(1): 230-238.
Ngata S. Simultaneous detemination of thiampenicol, florfenico, and chloramphenicol residues in muscles of animals and cultured fish by liquid chromatography[J]. Liquid chromatography, 1992,15(12):2045-2056.
Nordmo R, Varma K J, Sutherland I H, et al.. Florfenicol in Atlantic salmon, Salmo salar L: field evaluation of efficacy against furunculosis in Norway[J]. J Fish Dis,1994,17:239?244.
Noriko I.Tissue levels of oxolincic acid after oral or intravascular administration to freshwater and seawater rainbow trout[J]. Aquaculture,1992,102:9-15.
Nouws J F M, Grondel J L, Boon J H, et al.. Pharmacokinetics of antimicrobials in some fresh water fish species[A]. In:Michel CM, Aldeman DJ(Eds),Chemotherapy in Aquaculture:from theory to reality. Paris:Office international epizootiology,1992 ,437-447.
Odd A R. Pharmacokinetics and Bioavailability of Flumequine and Oxolinic Acid after Various Routes of Administration to Atlantic Salmon in seawater[J]. Aquaculture,1993,110: 207-220
Park B K, Lim J H, Kim M S, et al.. Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus)[J]. J.vet. Pharmacol.Therap,2006, 29:37-40.
Pinault L P, Millot L K, Sanders P J. Absolute oral bioavailability and residues of florfenicol in the rainbow trout(Oncorynchus mykiss)[J]. J Vet Pharmacol Therap,1997,20,SI:297-298.
Plakas S M. Determination of Flumequine in Channel Catfish by Liquid Chromatography with Fluorescence Detection[J]. Journal of AOAC International,1999,83(3):614-619.
Poher I, Blanc G. Pharmacokinetics of a discontinuous absorp tion of oxolinic acid in turbot, Scophthalmus maximus, after a single rapid oral administration[J]. Xenobiotica,1998,(28): 1061-1073.
Rodgers C J, Furones M D. Disease problems in cultured marine fish in Mediterranean[J]. Fish Pathology,1998,33(4):157-164.
Rupp H S.Stimultaneous Determination of Nitrofurazone and Furazonlidone in Shrimp(pen -aeus vannamei)Muscle Tissue by Liquid Chromatography with UV Detection[J]. Journal of AOAC iternational,1993,76(6):1235-1239.
Samuelsen O B, Hjeltnes B, Glette J. Efficacy of orally administered florfenicol in the treatment of furunculosis in Atlantic salmon[J]. J Aquat Anim Health,1998,10:56?61.
Samuelsen O B, Ervik A.Pharmacokinetics of florfenicol in cod Gadus morhua and in vitro antibacterial activity against Vibrioangmnum[J]. Dis Aquat Organ,2003,56:127-133.
Samuelsen O B, Lunestad B T, Jelmert A. Pharmacokinetic and efficacy studies on bath-administering potentiated sulphonamides in Atlantic halibut, Hippoglossus hippoglossus L.[J]. JFishDis,1997,20(4):287-296.
Snieszko S F, Friddle S O, Griffin P J. Successful treatment of ulcerdisease in brook trout (Salvel -inus fontinalis) with Terramycin[J]. Science,1951,113:717-718.
Stoffegren D A, Wooster G A, Bustos P S, et al.. Multiple route and dose pharmacokinetics of enrofloxacin in juvenile atlantic salmon[J]. Vet.Pharmacol.Ther.,1997,20 (2):111-123.
Ueno R. Pharmacokinetics and bioavailability of sulfamonomethoxine in cultured eel[J]. Fish Pathology,1998,33(4):297-301.
Uno K, Aoki T,Ueno R.Pharmacokinetic study of oxytetracycline in cultured rainbow trout, amago salmon, and yellowtail [J].Nippon Suisan Gakkaishi Bull,1992,58 (6):1151-1156.
Uno K, Aokin T, Ueno R, et al.. Pharmacokinetics and metabolism of sulphamonomethoxine in rainbowtrout (Oncorhynchus mykiss) and yellowtail(Seriolaquin queradiata) following bolus intravascular administration[J]. Aquaculture,1997,153(1):1-8.
Uno.K. Pharmacokinetics study of oxytetracycline in healthy and vibriosis-infected ayu (PlecoKlossus altimlis)[J]. Auaculture,1996,143:33-42.
Walker C C. Extraction and liquid chromatographic analysis of sulfadimethoxine and 4-N-Acetyl-sulfadimethoxine residues in channel catfish (Ictalurus Punctatus) muscle and plasma [J]. Journal of AOAC International,1994,77(6):1460-1466.
Wrzesinski C, Crouch L, Gaunt P, et al.. Florfenicol residue depletion in channel catfish, Ictalurus punctatus(Rafinesque)[J]. Aquaculture,2006, 253:309-316.
Yang X L, Liu Z Z, Masahito Y. Pharmacokinetics of cip rofloxacin in Chinese mitten-handed crab ( Eriocheir sinensis).Acta Hydrobiologica Sinica,2003,27(1):18-22.
Zhang Z D, Zhan W B, Xue Y H, et al.. Variations of granular haemocytes when shrimp Litopen-aeus vannamei infected by white spot syndrome virus(WSSV)[J]. Oceanologia et Limnologia Sinica,2005,36(1):67-71.
蔡雪峰,罗琳,李素珍,等.日本沼虾血细胞的初步研究[J].水生生物学报,2000,24(3):289–292.
陈眷华,彭羽.氯霉素类抗生素药物对人类健康的威胁[J].贵州畜牧兽医,2006,30(4):17–18.
陈四清.饲喂土霉素对鲤鱼生长及代谢残留的研究[J].饲料工业,1997,18(5):19–20.
陈文银,印春华.诺氟沙星在中华鳖体内的药代动力学研究[J].水产学报,1997,21(4):434–437.
陈晓慧,刘阳春,焦阳.氟苯尼考的研究新进展及其应用[J].现代畜牧兽医,2006,51(4):51-54.《动物性食品中兽药最高残留限量》,中华人民共和国农业部公告第235号.
杜向党,阎若潜,沈建忠.氯霉素类药物耐药机制的研究进展[J].动物医学展,2004,25(2):27-29.
樊甄姣,杨爱国,吕振明,等.鳗弧菌注射对栉孔扇贝免疫活性的影响[J].南方水产,2007,3(6):52-55.
方星星,李健,王群,等.复方新诺明在花鲈体内的残留及消除规律[J].海洋科学,2003,(9):18-20.
房文红.斑节对虾血淋巴中诺氟沙星含量测定及药代动力学[J].水生生物学报,2003,27(1):13-17.
冯敬宾,李刘冬,贾晓平.氟苯尼考在罗非鱼体内的药物动力学[J].南方水产,2006,2(5):25-29.
冯守明,杨先乐,李军,等.凡纳滨对虾白斑综合征血液病理研究[J].水产学报,2006,30(1):108-112.
郭闯,朱国强,王永坤,等.14株患病水生动物气单胞菌属细菌的分离鉴定与最佳治疗药筛选试验[J].水产科学,2003,22(4):14-17.
洪振涛.气相色谱法测定动物组织中氯霉素的残留量[J].中国兽药杂志,2006,40(2):14-16.
胡顶飞,沈建忠,吴先爱,等.氟苯尼考静注及肌注在鸡体内药代动力学研究[J].畜牧兽医学报,2002,33(4):384-388.
胡功政,苑丽,刘智明,等.氟苯尼考及其与多西环素联合的体外抗菌作用[J].中国兽医学报,2004,24(4):379-383.
黄显会,陈杖榴,张淑婷,等.禽多杀性巴氏杆菌感染对麻保沙星在鸡体内药动学特征的影响研究[J].畜牧兽医学报,2003,34(1):98-102.
黄志坚,何建国.鲑点石斑鱼细菌病原的分离鉴定和致病性[J].中山大学学报(自然科学版),2002,41(5):64-67.
金珊,蔡完其,王国良,等.养殖大黄鱼细菌性疾病的病原研究[J].浙江海洋学院学报(自然科学版),2002,21(3):225-230.
李爱华.氯霉素在草鱼和复合四倍体异育银鲫体内的比较药代动力学[J].中国兽医报,1998,18(4):372-374.
李建勇,赵荣材.我国兽医药物代谢动力学研究进展[J].中国兽药杂志,1999,33(4):44- 47.
李健,王群,孙修涛,等.噁喹酸对水生生物细菌病的防治效果及残留研究[J].中国水产学,2001,(3):45-49.
李静云,李健,王群,等.氟苯尼考3种不同给药方式在中国明对虾体内的药代动力学研究[J].海洋科学,2006,30(7):64-68.
李静云,李健,王群,等.磺胺间甲氧嘧啶在中国对虾体内的药代动力学研究[J].海洋水产研究,2006,27(4):6-11.
李静云,王群,李健,等.氟苯尼考在中国对虾组织内的代谢动力学及残留消除规律[J].水产学报,2004,28:63-68.
李兰生,王勇强.氯霉素在对虾体内的动力学研究[J].色谱,1997,15(5):431-434.
李美同,郭文林,郑国兴,等.土霉素在鳗鲡组织中残留的消除规律[J].水产学报,1997,21(1):39-43.
李秀波,沈建忠,胡顶飞,等.氟苯尼考静注及肌注在绵羊体内的药代动力学研究[J].畜牧兽医学报,2003,34(6):609-612.
李秀波,石波,梁萍.新型广谱抗菌药――氟苯尼考[J].国外畜牧科技,1999,(3):50-52.
李正,杨勇,杨先乐,等.盐酸环丙沙星药液口灌在中华绒螯蟹体内的代谢动力学研究[J].水产学报,2004,28 (增):25-29.
李佐卿,倪梅林,章再婷,等.高效液相色谱法检测水产品中喹诺酮类药物残留[J].现代科学仪器,2006,(3):70-71.
梁文权.生物药剂学与药物动力学[M].北京:人民卫生出版社,2004.
梁增辉,林黎明,刘靖靖,等.噁喹酸和氟甲喹在鳗鱼体内的药代动力学研究[J].海洋水产研究,2006,27(3):86-92.
廖昌容,徐力文,陈毕生,等.氟苯尼考对六种海洋致病弧菌的体外抗菌活性研究[J].水产养殖,2005,26(4):1-4.
刘涤洁,冯淇辉,陈杖榴,等.恩诺沙星在健康及实验性感染乳房炎奶山羊间的比较药动学[J].中国农业科学,2003,36(9):1100-1104.
刘彦,李健,王群,等.达氟沙星在健康和鳗弧菌感染牙鲆体内的药物代谢动力学比较[J].水产学报,2006,30(4):509-514.
刘彦,李健,王群,等.鳗弧菌感染牙鲆药物代谢动力学模型的初步建立[J].海洋水产研究,2007,28(2):76-83.
刘永涛,艾晓辉,杨红.不同水温下氟甲砜霉素在斑点叉尾鮰体内的药代动力学研究[J].水生生物学报,2009,(1):1-6.
刘玉林,王翔凌,杨先乐,等.诺氟沙星在大黄鱼体内的药代动力学及残留研究[J].水产学报,2007,31(5):655–660.
刘元元.药物动力学及药物动力学的新进展[J].河北农业科技,2008,12(9):168-170.
骆永泉,邓绍基.氟苯尼考防治猪传染性胸膜肺炎与链球菌病效果观察[J].养猪,2004,(2):53.
毛芝娟,卓华龙.锯缘青蟹细菌性传染病的病原菌研究[J].水产科学,2001,20(1):8-11.
孟勇,吴光红,朱晓华,等.RP-HPLC同时测定中华绒螯蟹肝脏中诺氟沙星、环丙沙星和恩诺沙星残留[J].中国水产科学,2005,(6):772-778.
农业部《新编渔药手册》编撰委员会.新编渔药手册[M].中国农业出版社,2005:318. NY5071-2002.中华人民共和国农业部,无公害食品渔用药物使用准则[S].
帕它木,黄贤仪,龚建福.氧化锂对小鼠脂质过氧化及抗氧化酶的影响[J].劳动医学(Labour Med),2000,17(1):25-26.
区炳庆,刘富来,潘燕琼,等.肠炎沙门氏杆菌感染雏鸭脾脏过氧化氢酶及过氧化物酶活性的变化[J].黑龙江畜牧兽医,2005,(3):11-13.
曲晓荣,王印庚,李胜忠,等.诺氟沙星在大菱鲆体内药代动力学及残留消除规律[J].海洋水产研究,2007,28(5):24-29.
苏成业.临床药物代谢动力学[M].北京:科学出版社,2003.
孙虎山,李光友.大肠杆菌感染后栉孔扇贝血淋巴中7种酶活力的变化[J].海洋科学,1999,(5):39-44.
谭志军,翟毓秀,冷凯良,等.呋喃西林和呋喃唑酮代谢物在大菱鲆组织中的消除规律[J].中山大学学报(自然科学版),2008,47(增刊):63-69.
唐俊,郑宗林,杨先乐,等.磺胺甲基异噁唑在中华绒螯蟹体内的代谢和消除规律[J].上海水产大学学报,2006,(4):449-455.
唐雪莲,佟恒敏.喹诺酮类药物研究进展及在兽医临床的应用问题[J].黑龙江畜牧兽医,2001,(3): 24-26.
唐雪莲,王群,李健.氯霉素在鲈鱼体内的药代动力学及残留的研究[J].海洋水产研究, 2003,24(2):45-50.
王国良,金珊,陈寅儿,等.三疣梭子蟹肌肉乳化病的病原及其致病性研究[J].海洋科学进展, 2006,24(4):526-531.
王国良,金珊,李政,等.三疣梭子蟹(Portunus trituberculatus)乳化病的组织病理和超微病理研究[J].海洋与湖沼,2006,37(4):297-303.
王丽平,陈绍峰,史晓丽,等.复方氟苯尼考口服液对人工诱发鸡大肠杆菌病的疗效试验[J].动物医学进展,2003,24(4):110-112.
王群.成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.
王群.氟苯尼考在中国对虾体内消除规律的研究[J].水产学报, 2004, 28(增):63-68.
王淑红,王艺磊,张朝霞,等.弧菌和大肠杆菌感染对杂色鲍无细胞血淋巴中几种酶活力的影响[J].中国水产科学,2004,11(1):37-40.
王武.我国水产养殖业的现状与发展趋势[J].渔业致富指南,2009,(7):12-17.
王志杰,冷凯良,孙伟红,等.水产品中氯霉素、甲砜霉素和氟甲砜霉素残留量高效液相色谱-串联质谱内标测定方法的研究[J].渔业科学进展,2009,(2):115-119.
王自然,朱文峰.氟苯尼考对耐氯霉素大肠杆菌菌株的体外药敏试验[J].中国家禽,2003,25(18):17.
谢剑华,管越强,王静波.虾青素对日本沼虾血细胞密度及吞噬活力的影响[J].河北渔业,2008,(1):8-13.
徐力文,廖昌容,王瑞旋,等.氟苯尼考在九孔鲍体内的药代动力学初步研究[J].台湾海峡, 2006,2:217-221.
杨成对,宋莉晖.对虾中氯霉素残留的分析方法研究[J].分析化学研究简报,2004,32(7):905-907.
杨先乐,刘至致,横山雅仁.盐酸环丙沙星在中华绒螯蟹体内的药物代谢动力学[J].水生生物学报,2003,27(1):18-22.
杨先乐,湛嘉,胡鲲.氯霉素在尼罗罗非鱼血浆中的药代动力学研究[J].水产学报, 2005,29(1):60-65.
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.
杨先乐,朱丽敏,林启存,等.肌注和口服氟苯尼考在中华鳖体内残留分析及药代动力学[J].水产学报,2006,30(4):515-519.
杨贤庆,李来好,郝淑贤,等.土霉素在凡纳滨对虾肌肉组织中残留情况的研究[J].热带海洋学报,2007,26(3):53-56.
叶雪珠,王小骊,赵燕申,等.水产品中氯霉素含量的快速检测与分析[J].食品科技,2003,(8):83-85.
叶燕玲,陈宽智.中国对虾(Penaeus chinesis)血细胞超微结构、分类及计数[J].青岛海洋大学学报,1993,23(2):35-42.
于占国,林风翱,卞正和,等.溶藻弧菌引起中国对虾红腿病的回接实验观察[J].海洋学报(中文版),1996,18(6):135-139.
余培建,翁祖桐,樊海平,等.氟苯尼考在欧洲鳗鲡体内的药物代谢动力学的研究[J].福建水产,2005,(4):54-57.
袁宗辉,廖小群,尹烨华,等.药物代谢动力学猪链球菌病模型的研制[J].畜牧兽医学报,1994,25(5):430-435.
战文斌,刘洪明,王越.水产养殖病害及其药物控制与水产品安全[J].中国海洋大学学报,2004,34(5):758-760.
张春玲,胡俊峰,王丕文,等.苯并(a)芘对鲫鱼肝脏总抗氧化能力的影响[J].环境与健康杂志,2004,21(5):325-326.
张培旗,李健,王群,等.磺胺甲基异噁唑在中国明对虾体内的残留和消除规律[J].水产科学,2005,24(11):17-20.
张收元,操继跃,罗宇良.氟苯尼考在鲫体内的药动学研究[J].水利渔业,2007,27(3):97-99.
张秀英,佟恒敏,姚春翥,等.单诺沙星在健康与支原体-大肠杆菌合并感染鸡体内的药动学研究[J].畜牧与兽医,2002,34(2):5-8.
张秀英.单诺沙星在健康和支原体-大肠杆菌感染鸡的药动学与药效学研究[D].东北农业大学, 2001.
张雅斌.不同给药方式下鲤鱼对诺氟沙星的药代动力学研究[J].水产学报,2000,24(6):559 -563.
张祚新,张雅斌,杨永胜,等.诺氟沙星在鲤鱼体内的药代动力学[J].中国兽医学报,2000,20(1):66-69.
郑宗林,刘鸿艳,黄辉,等.复方新诺明在罗氏沼虾中的药代动力学和组织分布[J].广东海洋大学学报,2008,28(4):54-59.
中华人民共和国药典委员会.中华人民共和国药典2000年版二部[S].北京:中国农业出版社:711-712.
朱秋华,钱国英.3种药物在甲鱼体内的残留研究[J].中国水产科学,2001,8(3):50-53.
朱忠勇.实用医学检验学[M].北京:人民军医出版社,1997:368-378.
Abedini S, Namdari R, Law F C P. Comparative pharmacokinetics and bicavailability of oxytetr-acycline in rainbow trout and chinook salmon following in traarterial administration[J]. Aquaculture,1998,162:23-32.
Baggot J D. Distribution of antimicrobial agents in normal and diseased animals[J]. J Am Vet Med Assoc,1980,176(10):1085-1090.
Bernt M, Tor E H, Kanval J V, et al..Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11℃[ J]. Aquaculture,1993,112:1-11.
Bjorklund H V. Temperature-ralated absorption and excretion of oxolinic acid in rainbow trout (Oncorhynchus mykiss)[J]. Aquaculture,1992,102(1):17-27.
BreganteM A, Abadia A R, Aramayoma J J, et al.. Phamacokinetics of enrofloxacin in rainbow trout after a single intravascular injection[J]. Actas Deliv Congreso Nactional de Acuicultura, Centrode Investigaciones Marinas, Pontevedr (Spain),1993,709-712.
Carignan G, Carrier K, Sved S. Assay of Oxytetracycline residues in salmon muscle by liquid chr-omatography with ultraviolet detection[J]. JAOACInt.,1993,76(2):325-328.
Carignan G.Assay of Oxolinic Acid Resudues in Salmon Muscle by Liquid Chromatography with Fluorescence Detection:Interlaboratory Study[J]. Journal of AOAC iternational,1991,74 (6):906-909.
Chue V, Larry J S,Guy R, et al.. Liquid chromatographic determination of florfenicol in the pla-sma of multiple species of fish[J]. Journal of Chromatography B,2002,780(1):111-117.
Cravedi J P. Digestibility of clorampheicol, oxolinic acid and oxytetracycline in rainbow trout and influence of these antibiotics on lipid digestibility[J]. Aquaculture,1987,60:133-141.
Damrongsak F, Ausa C, Sommai C, et al..Bioavailability and absorption analysis of oxytetracycl-ine orally administered to the standardized moulting farmed Pacific white shrimps (Penaeus vannamei)[J]. Aquaculture,2007,(269):89–97.
Dario L,Laura F,Emilio G,et al.. Long depletion time of enrofloxacin in rainbow trout (Oncorhync-hus mykiss)[J]. Antimicrobial Agents and Chemot herapy,2004,48(10):3912-3917.
Elema M O. Bioavailability of oxtetrycline from medicated feed administered to atlantic salmon (Salmo salar L .) in seawater[J]. Aquaculture,1996,143:7-14.
FAO 2002. Antibiotic residues in aquaculture products, The State of World Fisheries andAquaculture 2002.
Feng T, Zheng W, Hong W,et al.. Effect of benzo(a)pyrene on antioxidant enzyme activities in Boleophthalmus pectinirostris live[J]. Ying Yong Sheng Tai Xue Bao,2001,12:422-424.
Fukui H, Fujihara Y, Kano Y. Invitro and in vivo antibacterial activities of florfennicol, a new fluorinated analog of thiamphenicol, against fish pathogens[J]. FishPathol,1987,22:201?207.
Gentleman M S. High-performance liquid chromatographic determination of sulphadiazine and trimethoprim in chinook salmon muscle tissue[J]. Journal of Chromatography,1993, 633.
George R, Ioannis N, Athanassios E T, et al.. Pharmacokinetics and bioavailability of oxytetracyc- line in gilthead sea bream (Sparus aurata) after a single dose[J].Aquaculture,2003,(221):75–83.
George R, Ioannis N, Maria A. Tissue distribution and residue depletion of oxolinic acid in gilthead sea bream (Sparus aurata) and sharpsnout sea bream (Diplodus puntazzo) following multiple in-feed dosing[J]. Aquaculture,2003,(224):245?256.
Grondel J L, Nouws J F M. Pharmacokinetics and tissue distribution of oxy- tetracycline in carp, cyprinus carpip L, follows different routes of administration[J]. Journal of Fish Disease,1987,10(3):153-163.
Heaton L H. Tissue Residue and Oral Safety of Fuurazolidone in Four Species of Trout [J]. Progr Fish-Culturist,1968,30:208-215.
Heijden H J. Plasma disposition of flumequine in common carp, African catfish and European eel after a single peroral administration[J]. Aquaculture, 1994, 123:21-30.
Herman R L, Degurse P E. Sulfamerazine residues in trout tissues[J]. Ichthyologica,1967,39:73-79.
Ho S P, Cheng C F, Wang W S. Pharmacokinetic and depletion studies of sarafloxac in after oral adminstration to eel (Anguilla anguilla)[J]. Journal of Veterinary Medical Science,1999,61 (5):459 -463.
Ho S P, Hsu T Y, Chen M H, et al.. Antibacterial effect of chloramphenicol, thiamphenicol and florfenicol against aquatic animal bacteria[J]. The Journal of Veterinary Medical Science, 2000,62:479-485.
Hormazabal V, Steffenak I, Yndestad M. Simutaneous extraction and determinition of residues of florfenicol and the metabolite florfenicol amine in fish tissues by high-performance liquid chromatography[J]. J Chromatogr,1993,616:161-165.
Horsberg T E, Hoff K A, Nordmo R. Pharmacokinetic of florfenicol and its metabolite florfenicol amine in Atlantic salmon[J]. Journal of Aquatic Animal Health,1996,8:292-301.
Horsberg T E, Martinsen B, Varma K J. The disposition of 14C-florfenicol in Atlantic salmon (Salmo salar)[J]. Aquaculture,1994,122:97?106.
Iwata K, Tanohara Y, Ishibashi O. Studies on factors related to mortality of young red seabream (Pagrus major)in the artfical seed production[J]. Fish pathology,1978,13:97-102.
Intorre L, Cecchini S, Bertini S, et al.. Pharmacokinetics of enrofloxacin in the seabass (Dicentrar-chus labrax)[J]. Aquaculture,2000,(182):49–59.
Lackie A M. Invertebrate immunity [J]. Parasitology,1980,80:393-412.
Lee K K. Pathogenesis studies on Vibrio alginolyticus in th grouper, Epinephelus malabaricus Bloch et Schneider [J]. Microbial Pathogenesis,1995,19:39-48.
Martinsen B. Single dose kinetic Study of sarafloxacin after intravenous and oral administra -tion of different formulations to Atlantic salmon (Salmo salar) held in sea water at 8.5 degree C[J]. Aquaculture,1993(118):37-47.
Martinsen B, Horsberg T E, Varma K J, et al.. Single dose pharmacokinetic study of florfenicol in Atlantic salmon in seawater at 11℃[J]. Aquaculture,1993,112:1-11.
Michel C M F. Pharmacokinetics and metabolism of sulfadimethoxine in channel catfish (Ictalurus punctatus)[J]. Dissertation abstracts international part B:science and engineering,1990,51(1): 230-238.
Ngata S. Simultaneous detemination of thiampenicol, florfenico, and chloramphenicol residues in muscles of animals and cultured fish by liquid chromatography[J]. Liquid chromatography, 1992,15(12):2045-2056.
Nordmo R, Varma K J, Sutherland I H, et al.. Florfenicol in Atlantic salmon, Salmo salar L: field evaluation of efficacy against furunculosis in Norway[J]. J Fish Dis,1994,17:239?244.
Noriko I.Tissue levels of oxolincic acid after oral or intravascular administration to freshwater and seawater rainbow trout[J]. Aquaculture,1992,102:9-15.
Nouws J F M, Grondel J L, Boon J H, et al.. Pharmacokinetics of antimicrobials in some fresh water fish species[A]. In:Michel CM, Aldeman DJ(Eds),Chemotherapy in Aquaculture:from theory to reality. Paris:Office international epizootiology,1992 ,437-447.
Odd A R. Pharmacokinetics and Bioavailability of Flumequine and Oxolinic Acid after Various Routes of Administration to Atlantic Salmon in seawater[J]. Aquaculture,1993,110: 207-220
Park B K, Lim J H, Kim M S, et al.. Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus)[J]. J.vet. Pharmacol.Therap,2006, 29:37-40.
Pinault L P, Millot L K, Sanders P J. Absolute oral bioavailability and residues of florfenicol in the rainbow trout(Oncorynchus mykiss)[J]. J Vet Pharmacol Therap,1997,20,SI:297-298.
Plakas S M. Determination of Flumequine in Channel Catfish by Liquid Chromatography with Fluorescence Detection[J]. Journal of AOAC International,1999,83(3):614-619.
Poher I, Blanc G. Pharmacokinetics of a discontinuous absorp tion of oxolinic acid in turbot, Scophthalmus maximus, after a single rapid oral administration[J]. Xenobiotica,1998,(28): 1061-1073.
Rodgers C J, Furones M D. Disease problems in cultured marine fish in Mediterranean[J]. Fish Pathology,1998,33(4):157-164.
Rupp H S.Stimultaneous Determination of Nitrofurazone and Furazonlidone in Shrimp(pen -aeus vannamei)Muscle Tissue by Liquid Chromatography with UV Detection[J]. Journal of AOAC iternational,1993,76(6):1235-1239.
Samuelsen O B, Hjeltnes B, Glette J. Efficacy of orally administered florfenicol in the treatment of furunculosis in Atlantic salmon[J]. J Aquat Anim Health,1998,10:56?61.
Samuelsen O B, Ervik A.Pharmacokinetics of florfenicol in cod Gadus morhua and in vitro antibacterial activity against Vibrioangmnum[J]. Dis Aquat Organ,2003,56:127-133.
Samuelsen O B, Lunestad B T, Jelmert A. Pharmacokinetic and efficacy studies on bath-administering potentiated sulphonamides in Atlantic halibut, Hippoglossus hippoglossus L.[J]. JFishDis,1997,20(4):287-296.
Snieszko S F, Friddle S O, Griffin P J. Successful treatment of ulcerdisease in brook trout (Salvel -inus fontinalis) with Terramycin[J]. Science,1951,113:717-718.
Stoffegren D A, Wooster G A, Bustos P S, et al.. Multiple route and dose pharmacokinetics of enrofloxacin in juvenile atlantic salmon[J]. Vet.Pharmacol.Ther.,1997,20 (2):111-123.
Ueno R. Pharmacokinetics and bioavailability of sulfamonomethoxine in cultured eel[J]. Fish Pathology,1998,33(4):297-301.
Uno K, Aoki T,Ueno R.Pharmacokinetic study of oxytetracycline in cultured rainbow trout, amago salmon, and yellowtail [J].Nippon Suisan Gakkaishi Bull,1992,58 (6):1151-1156.
Uno K, Aokin T, Ueno R, et al.. Pharmacokinetics and metabolism of sulphamonomethoxine in rainbowtrout (Oncorhynchus mykiss) and yellowtail(Seriolaquin queradiata) following bolus intravascular administration[J]. Aquaculture,1997,153(1):1-8.
Uno.K. Pharmacokinetics study of oxytetracycline in healthy and vibriosis-infected ayu (PlecoKlossus altimlis)[J]. Auaculture,1996,143:33-42.
Walker C C. Extraction and liquid chromatographic analysis of sulfadimethoxine and 4-N-Acetyl-sulfadimethoxine residues in channel catfish (Ictalurus Punctatus) muscle and plasma [J]. Journal of AOAC International,1994,77(6):1460-1466.
Wrzesinski C, Crouch L, Gaunt P, et al.. Florfenicol residue depletion in channel catfish, Ictalurus punctatus(Rafinesque)[J]. Aquaculture,2006, 253:309-316.
Yang X L, Liu Z Z, Masahito Y. Pharmacokinetics of cip rofloxacin in Chinese mitten-handed crab ( Eriocheir sinensis).Acta Hydrobiologica Sinica,2003,27(1):18-22.
Zhang Z D, Zhan W B, Xue Y H, et al.. Variations of granular haemocytes when shrimp Litopen-aeus vannamei infected by white spot syndrome virus(WSSV)[J]. Oceanologia et Limnologia Sinica,2005,36(1):67-71.