6 : 1123 (16±0.6), 29, ph 8.2,,,, 2, 试验药品与试剂 ( 98.0%, ), Sigma ; ( 99.7%, ), ; ( 5 g/100 ml, KP04LE-1), (), 85% 试验仪器 Agilent1100 (HP

Size: px

Start display at page:

Download "6 : 1123 (16±0.6), 29, ph 8.2,,,, 2, 试验药品与试剂 ( 98.0%, ), Sigma ; ( 99.7%, ), ; ( 5 g/100 ml, KP04LE-1), (), 85% 试验仪器 Agilent1100 (HP"

卞束
7 years ago
Views:

1 34 6 Vol. 34, No ACTA HYDROBIOLOGICA SINICA Nov., DOI: /SP.J ,2 梁俊平李 2 健张 2 喆王 2 群 2 刘德月 1 王吉桥 (1., ; 2.,, ) : (16±0.6), 20 mg/kg,, DAS2.0, (Scophthalmus maximus),,, C =10.237e 0.702t e 0.01t e t C =3.701e 0.072t e 0.007t 7.235e 0.364t, t 1/2Ka (0.027h) t max (0.5h) t 1/2α (0.987h) t 1/2β (68.003h) (1.904h 4h 9.621h h), C max ( μg/ml) F (88.57%) ( μg/ml 66.42%),,, :, mg/kg, 2, 2 3 ;, mg/kg, 1, 3 5, 30d 45d : ; ; ; ; 中图分类号 : S948 文献标识码 : A 文章编号 : (2010) (Scophthalmus maximus) 1992,,,,,, (Enrofloxacin), (Vibrio anguillarum) (Aeromonas hydrophila) (Aeromonas salmonicida) (Vibrio salmonicida), [1 4] (Dicentrarchus labrax) (Oncorhynchus mykiss) (Salmo salar) (Colossoma brachypomum) (Cyprinus carpio) (Fenneropenaeus chinensis)(eriocheir sinensis) (Anguilla anguilla) [5 12],,, (Pharmacokinetics, PK)(Pharmacodynamics, PD),, 试验动物, (157.4±8.5) g, 收稿日期 : ; 修订日期 : 基金项目 : ( ); (nyhyzx07-046) 作者简介 : (1981 ),, ; ; Liangjunpinglover@163.com 通讯作者 :,, ; Tel: ; Lijian@ysfri.ac.cn

2 6 : 1123 (16±0.6), 29, ph 8.2,,,, 2, 试验药品与试剂 ( 98.0%, ), Sigma ; ( 99.7%, ), ; ( 5 g/100 ml, KP04LE-1), (), 85% 试验仪器 Agilent1100 (HPLC), WindowsNT4.0 HP, KL512, XHF-1, Eppendorf 1.2 给药与采样 :,,, 20 mg/kg min h, 6, 1%, 4000 r/min 10min,, 20 :,,, 30 40, 20 mg/kg min h, 6, 1%, 4000 r/min 10min,, 20, 5 g,, 6 20 :, 1 ml (), 20 样品处理 :, 1 ml 10 ml, 4 ml 10s, 2h, 5000 r/min 10min,, 40, 1 ml, 0.22 μm :, 1 g (), 2 ml r/min 20s; 2 ml, 10s, 2h, 5000 r/min 10min,, 40, 1 ml, 2 ml, 0.22 μm 标准曲线与最低检测限 0.01 g, NaOH, 100 ml, 100 μg/ml, μg/ml HPLC,,, [13] 回收率和精密度的测定 μg/ml 1 g 1 ml,, 3,, 样品实测药物浓度回收率 = 100% 样品理论药物浓度 1d 5, 5d, (C V%), 色谱条件 : Agilent Tc-C 18 (250 mm 4.6 mm, 5 µm); : :(0.01 mol/l, ph 3.42)=20:80 (v:v);, 278 nm, 460 nm; 30 ; 1.0 ml/min; 20 μl 数据处理 DAS2.0, 1 1/C 1/C 2 3, AIC R 2, 休药期的计算, : C i = C 0 e βt, (MRL),

3 : Ln( C0 / MRL) T = β μg/ml, : Y= X , R 2 = μg/ml 2.2, μg/ml, 87.70% 94.64% 80.42% 90.02% 80.94% 87.78% 81.96% 94.24% ( 1); 0.29% 2.03%, 2.06% 5.10%, 70%, 10%,, 2.3 房室模型及药代动力学参数 DAS2.0 3,,, : C=Ae αt +Be βt ;,, : C=Ae αt + Be βt (A B)e Kat ( 2) 表 1 恩诺沙星在血浆和各组织中的回收率 Tab. 1 Recovery of enrofloxacin in plasma and tissue of Scophthalmus maximus Concentration Recovery (%) (μg/ml) Plasma Muscle Liver Kidney ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±3.04 表 2 大菱鲆静注肌注和口服恩诺沙星的药代动力学参数 Tab. 2 Pharmacokinetic parameters of enrofloxacin following intravenous, intramuscular and oral administration of 20 mg/kg b.w to Scophthalmus maximus Routes of administration Parameters Unit Intravenous administration Intramuscular administration Oral administration A μg/ml B μg/ml α 1/h β 1/h Ka 1/h t 1/2Ka h t 1/2α h t 1/2β h K 10 1/h K 12 1/h K 21 1/h AUC 0-t h μg/ml AUC t max h C max μg/ml Vd L/kg F %

4 6 : 1125 : C = e t e t C = e t e 0.01 t e t C = 3.701e t e t e t 恩诺沙星在大菱鲆体内的吸收与分布, - ( 1 3) 3 - Fig. 3 Mean enrofloxacin concentration in tissue of Scophthalmus maximus after oral administration of 20 mg/kg 1 - Fig. 1 Mean enrofloxacin concentration in plasma of Scophthalmus maximus after intravenous intramuscular and oral administration of 20 mg/kg 2 - Fig. 2 Mean enrofloxacin concentration in tissue of Scophthalmus maximus after intramuscular administration of 20 mg/kg 恩诺沙星在各组织中的消除规律, 3 (C) (t) ( 3) μg/kg, 200 μg/kg FDA [14],, 30.25d 21.09d 16.93d, 45.34d 42.07d 25.22d,,,, 30d, 45d 表 3 大菱鲆肌注口服恩诺沙星后各组织消除相曲线方程及参数 Tab. 3 The equation of elimination curve and parameters of enrofloxacin in tissue following intramuscular and oral administration of 20 mg/kg b.w of enrofloxacin to Scophthalmus maximus Tissue Equation R 2 β (h) t 1/2β Muscle Liver Kidney C = e t C = e t C = e t C = e t C = e t C = e t

5 , (1.0h)(1.72h) [9,15], (0.5h) [16], [10,11,17], ; (6.03h) (6.0h) 蠵 (7.0h) [5,7,18], (2.0h) (1.2441h) (1.5h) [12,19,20],,, Kwasi Bugyei W D, et al. [21] 5 mg/kg, 0.79h 2.5h; Lewbart G, et al. [8] 5 mg/kg, 4h 36h,,,, ;,,,,, (F) 88.57%, 66.42%, [22] F 65.97% 49.44%, [6,7] F 55.5% 42%,, [15,23], 3.2 2,,, 2 3,,,,,, [24] 3.3 (6.39h)(10.6h) (1.97h) (4.70h) [15,21,25,26], (52.39h)) (69.315h) [11,17] ; (6.80h) (6.93h) ( 6.03h, 5.24h) (6.4h) [15,23,27,28], (105.11h) [22],,,,,, Bailey T A, et al. Stoffregen D A, et al. [15,22],, 3.4,, [29], (V. anguillarum) μg/ml, (A. hydrophila) 0.5 μg/ml, (A. salmonicida) 0.60 μg/ml, (V. salmonicida) 0.60 μg/ml [1 4], PK-PD, C max /MIC AUC 0 24 /MIC, C max /MIC 8 AUC 0 24 /MIC 100,, C max /MIC=10 [30 32],, C max /MIC AUC 0 24 /MIC , C max /MIC AUC 0 24 /MIC ,,,, [33] : C ss =F X 0 /(V d

6 6 : 1127 K 10 τ), C ss : ; F: ; X 0 : ; V d : ; K 10 : ; τ:, 10 MIC,, mg/kg, 2, 2 3 ;, mg/kg, 1, 3 5 4, PK-PD,,,,,, ;,,,, ;,,,, : [1] Bernt Martinsen, Hanne Oppegaard, Reidun Wichstrøm, et al. Temperature-dependent in vitro antimicrobial activity of four 4-quinolones and oxytetracycline against bacteria pathogenic to fish [J]. Antimicrobial Agents Chemotherapy, 1992, 36(8): [2] Maluping R P, Lavilla-Pitogo C R, DePaola A, et al. Antimicrobial susceptibility of aeromonasspp., Vibrio spp. and plesiomonas shigelloides isolated in the Philippines and Thailand [J]. International Journal of Antimicrobial Agents, 2005, 25(4): [3] Paulr Bowser, Gregorya Wooster and Hui-Min Hsu. Laboratory efficacy of enrofloxacin for the control of Aeromonas salmonicida infection in Rainbow Trout [J]. Journal of Aquatic Animal Health, 1994, 6: [4] Della Rocca G, Di Salvo A, Malvisi J, et al. The disposition of enrofloxacin in Seabream (Sparus aurata L.) after single intravenous injection or from medicated feed administration [J]. Aquaculture, 2004, 232: [5] Intorre L, Cecchini S, Bertini S, et al. Pharmacokinetics of enrofloxacin in the Seabass (Dicentrarchus labrax) [J]. Aquaculture, 2000, 182: [6] Bowser P R, Wooster G A, Stleger J, et al. Pharmacokinetics of enrofloxacin in fingerling Rainbow Trout (Oncorhynchus mykiss) [J]. Journal of Veterinary Pharmacology and Therapeutics, 1992, 15(1): [7] Bernt Martinsen, Tor Einar Horsberg. Comparative single-dose pharmacokinetics of four quinolones, oxolinic acid, flumequine, sarafloxacin and enrofloxacin, in Atlantic Salmon (Salmo salar) held in seawater at 10 [J]. Antimicrobial Agents and Chemotherapy, 1995, 39(5): [8] Lewbart G, Vaden S, Deen J, et al. Pharmacokinetics of enrofloxacin in the Red Pacu (Colossoma brachypomum) after intramuscular, oral and bath administration [J]. Journal of Veterinary Pharmacology and Therapeutics, 1997, 20: [9] Pareeya Udomkusonsri, Surapong Arthitvong, Narumol Klangkaew, et al. Pharmacokinetics of enrofloxacin in Koi Carp (Cyprinus carpio) after various routes of administration [J]. Kasetsart Journal (Nature Science), 2007, 41: [10] Fang X X, Wang Q and Li J. Pharmacoknetics of enroflxacin and its metabolite ciprofloxacin in Fenneropenaeus chinensis [J]. Journal of Fisheries of China, 2004, 28(suppl.): [,,.., 2004, 28(): 36 41] [11] Wu G H, Meng Y, Zhu X H, et al. Pharmacokinetics and tissue distribution of enrofloxacin and its metabolite ciprofloxacin in the Chinese mitten-handed crab, Eriocheir sinensis [J]. Analytical Biochemistry, 2006, 358: [12] Fang W H, Yu H J, Cai Y Q, et al. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in European eel (Anguilla anguilla) after a single oral gavage [J]. Journal of Fishery Sciences of China, 2007, 14(4): [,,,.., 2007, 14(4): ] [13] Wang X L, Fang Z P, Cao J Y, et al. Studies on residue and depletion of sarafloxacin hydrochloride in Goldfish, Carassius auratus [J]. Acta Hydrociologica Sinica, 2006, 30(2): [,,,.., 2006, 30(2): ] [14] Vranic M L, Marangunich L, Fernández Courel H, et al. Estimation the withdrawal period for veterinary drugs used in food producing animals [J]. Analytic Chimica Acta, 2003, 483(1-2): [15] Bailey T A, Sheen R S, Silvanose C, et al. Pharmacokinetics of enrofloxacin after intravenous, intramuscular and oral administration in Houbara Bustard (Chlamydotis undulate

7 macqueenii) [J]. Journal of Veterinary Pharmacology and Therapeutics, 1998, 21: [16] Bonnie L. Raphael, Mark Papich and Robert A. Cook. Pharmacokinetics of enrofloxacin after a single intramuscular injection in Indian Star Tortoises (Geochelone elegans) [J]. Journal of Zoo and Wildlife Medicine, 1994, 25(1): [17] Qian Y Y, Tang J, Zheng Z L, et al. Pharmacokinetics of enrofloxacin in Macrobrachium rosenbegii [J]. Chinese Journal of Zoology, 2007, 42(5): [,,,.., 2007, 42(5): 62 69] [18] Elliott Jacobson D.V.M, Ph.D, Dipl. A.C.Z.M, et al. Plasma concentration of enrofloxacin after single-dose oral administration in Loggerhead Sea Turtles (Curetta caretta) [J]. Journal of Zoo and Wildlife Medicine, 2005, 36(4): [19] Zhang Y B, Liu Y H, Zhang Z X, et al. Pharmacodynamic of enrofloxacin in Carps [J]. Journal of Dalian Fisheries University, 2004, 19(4): [,,,.., 2004, 19(4): ] [20] Jian J C, Wu Z H and Chen G. Pharmacokinetics of enrofloxacin in Sciaenop socellatus [J]. Chinese Journal of Veterinary Science, 2005, 25(2): [,,.., 2005, 25(2): ] [21] Kwasi Bugyei, Black W D and Scott McEwen. Pharmacokinetics of enrofloxacin given by the oral, intravenous and intramuscular routes in Broiler Chickens [J]. Canadian Journal of Veterinary Research-revue Canadienne de Recherche Veter, 1999, 63: [22] Stoffregen D A, Wooster G A, Bustos P S, et al. Multiple route and dose pharmacokinetics of enrofloxacin in juvenile Atlantic Salmon [J]. Journal of Veterinary Pharmacology and Therapeutics, 1997, 20(2): [23] Zeng Z L, Feng Q H. Pharmacokinetics and bioavailability of enrofloxacin in pigs [J]. Chinese Journal of Veterinary Science, 1996, 16(6): [,.., 1996, 16(6): ] [24] Deng S H, Zhang X Z and Zhou L J. Pharmacokinetics and Biopharmaceutics (First Edition) [M]. Tianjin: Tianjin Science and Technology Translation and Publishing Company. 1992, [,,. ( 1 ). :. 1992, ] [25] Verma H K, Pangawkar G R, Chaudhary R K, et al. Pharmacokinetics and dosage regimen of enrofloxacin in Buffalo Bulls after intramuscular administration [J]. Veterinary Research Communications, 1999, 23(8): [26] Muammer Elmas, Bunyamin Tras, Sezai Kaya, et al. Pharmacokinetics of enrofloxacin after intravenous and intramuscular administration in Angora Goats [J]. The Canadian Journal of Veterinary Research, 2001, 65: [27] Dimitrova D J, Lashev L D, Yanev St. G, et al. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in male and female Turkeys following intravenous and oral administration [J]. Veterinary Research Communications, 2006, 30(3): [28] Linnehan R M, Ulrich R.W and Ridgway S. Enrofloxacin serum bioactivity in Bottlenose Dolphins, Tursiops truncatus, following oral administration of 5 mg/kg in whole fish [J]. Journal of Veterinary Pharmacology and Therapeutics, 1999, 22(3): [29] Zhang Z, Wang Y G, Yang G P, et al. The status of research on bacterial diseases of Turbot Scophthalmus maximus [J]. Transactions of Oceanology and Limnology, 2004, (3): [,,,. (Scophthalmus maximus)., 2004, (3): 83 89] [30] Forrest A, NixD E, Ballow C H, et al. Pharmacok dynam of intravenous ciprofloxacin in seriously ill patients [J]. Antimicrob Agents Chemother, 1993, 37 (5): [31] Marra F, Partovi N and Jewesson P. Aminoglycoside administrations as a single daily dose: an improvement to current practice or a repeat of previous errors [J]? Drugs, 1996, 52 (3): [32] Shojaee AliAbadi F, Lees P. Antibiotic treatment for animals: effect on bacterial population and dosage regimen optimization [J]. International Journal of Antimicrobial Agents, 2000, 14(4): [33] Xu S Y, Bian R L and Chen X. Pharmacology Experimental Methods (Third Edition) [M]. Beijing: People s Medical Publishing House. 2002, [,,. ( 3 ). :. 2002, ]

8 6 : 1129 PHARMACOKINETICS OF ENROFLOXACIN IN TURBOT (SCOPHTHALMUS MAXIMUS) AFTER A SINGLE INTRAMUSCULAR AND ORAL ADMINISTRATION LIANG Jun-Ping 1,2, LI Jian 2, ZHANG Zhe 2, WANG Qun 2, LIU De-Yue 2 and WANG Ji-Qiao 1 (1. College of Life Sciences and Biotechnology, Dalian Ocean University, Dalian ; 2. Key Laboratory for Sustainable Utilization of Marine Fishery Resources Ministry of Agriculture, Yellow Sea Fisheries Institute, Chinese Academy of Fishery Sciences, Qingdao , China) Abstract: Turbot (Scophthalmus maximus) is a traditionally farmed species in Europe. Although it was introduced to China in 1992, it has become an important aquaculture species in coastal areas of northern China, especially in the Jiaodong Peninsula, Shandong Province. Recently, more and more epizootic diseases of farmed turbot in China occurred because of high density stocking and improper management. Enrofloxacin, a third-generation member of the quinolone family, it has been also used widely to prevent or treat bacterial diseases in fish farming in many countries. And it has previously been studied in Seabass (Dicentrarchus labrax), fingerling Rainbow Trout (Oncorhynchus mykiss), Atlantic Salmon (Salmo salar), Red Pacu (Colossoma brachypomum) and Koi Carp (Cyprinus carpio), ect. However, to our knowledge, there are no studies concerning the pharmacokinetics of enrofloxacin in turbot. So the purpose of this study was to compare the pharmacokinetics of enrofloxacin in plasma of turbot after intramuscular and oral administration to establish the scheme of enrofloxacin, at the water temperature of (16±0.6), and generate data in muscle, liver and kidney to establish a reasonable withdrawal period for enrofloxacin in farmed turbot. Six turbot were randomly selected from the tank and sampled at 5, 15, 30min and 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96h after the last intramuscular and oral administration, respectively. The concentration of enrofloxacin were determined by the High Performance Liquid Chromatography, the isocratic mobile phase consisted of a phosphoric acid (0.01mol/L)-acetonitrile (80:20 v:v), adjusted to ph 3.42 with triethylamine, at a flow-rate of 1mL/min. The agilent Tc-C 18 (5μm, mm) was used and the fluorescence detector was set at 278 nm and 460 nm as excitation and emission wavelengths, respectively. The percentage recoveries of enrofloxacin were all higher than 81.16% for plasma, liver, kidney and muscle, the intra-day precision of the analytical method for samples (three replications) was 0.29% 2.03%, the inter-day precision was 2.06% 5.10%, the detection limits of enrofloxacin was 0.01μg/g (μg/ml). The data were analyzed with the pharmacokinetic program DAS2.0. The results showed that the plasma concentration-time data for enrofloxacin were best described as a two-compartment open model with first-order absorption and elimination after intramuscular and oral administration, the pharmacokinetic equation was: C im = e 0.702t e 0.01t e t and C po = 3.701e 0.072t e 0.007t 7.235e 0.364t, respectively. After administration by intramuscular and oral, the main pharmacokinetic parameters were as follows: t 1/2Ka 0.027h and 1.904, t max 0.5h and 4h, t 1/2α 0.987h and 9.621h, C max μg/mL and μg/mL, F 88.57% and 66.42%, t 1/2β h and h, respectively. It indicated that more quickly absorption, higher peak plasma concentration, higher bioavailability and faster elimination after intramuscular administration than by oral administration. It was found that those two routes of enrofloxacin administration to turbot were effective since the concentrations of drug in plasma were greater than minimal inhibitory concentration of most fish bacterial pathogens, under this experiment condition. The scheme of enrofloxacin was established to fish bacterial diseases, with the dose of 19.05mg/kg at the interval of 2d, by intramuscular; and 13.92mg/kg at the interval of 1d, by oral administration. As an edible tissue, muscle was selected as target tissue in the experiment, the withdrawal periods, which should not be less than 30d and 45d flowing intramuscular and oral administration, respectively, was established according to the MRL by using elimination parameters and equations. Key words: Scophthalmus maximus; Enrofloxacin; Pharmacokinetics; Dosage regimen; Withdrawal period

Microsoft Word - 李晖_news_.doc

Microsoft Word - 李晖_news_.doc 肌注和口服药饵麻保沙星在日本对虾体内的药代动力学比较李晖 1, 李健 2, 孙铭 2 2, 梁俊平 (1., 261053; 2., 266071) 摘要 : 在水温 (25±0.6) 条件下, 分别以 10 10 和 30 mg/kg 剂量给健康日本对虾血窦注射肌注和口服药饵麻保沙星后, 用高效液相色谱法测定药物浓度, 采用 DAS2.0 药动学软件对血药浓度进行分析, 主要比较了肌注和口服药饵两种给药方式下麻保沙星在日本对虾体内的药代动力学差异