本論文的研究目的係以安默西林(amoxicillin)注射黑鯛(Acanthopagrus schlegelii)，觀察注射安默西林後不同時間點下黑鯛血漿、肌肉及肝臟組織中殘留情形，並觀察安默西林是否對黑鯛白血球的超氧陰離子、化學發光反應、吞噬率、吞噬指數及血清中白蛋白、球蛋白及白蛋白-球蛋白等非特異性免疫反應有所影響。
結果顯示，安默西林在黑鯛血漿及肝臟樣品中的最大殘留濃度皆出現在注射後第1小時(第一個採樣點) ，濃度分別為82.53 μg/ml、34.20 μg/g，隨後殘留濃度皆隨著時間增加而降低。安默西林在黑鯛肌肉樣品中的殘留濃度亦隨時間增加而增加，注射後第4小時達最大殘留，濃度為2.99μg/g，隨後殘留濃度隨時間增加而降低。安默西林在三種樣品中殘留濃度減少的量依序為血漿＞肝臟＞肌肉。黑鯛血漿中安默西林殘留濃度數據符合藥物動力學二室模式，以雙指數方程式計算(C = Ae-αt+Be-βt)，可得一方程式表示C = 94.15e-0.24t+8.76e-0.07t，k12、k21、kel分別為0.03、0.08、0.21 (h-1)，根據藥物動力學各項參數，推測大部份amoxicillin在中央室已排除，並未進入周圍室。非特異性免疫方面，黑鯛經注射安默西林後，黑鯛白血球超氧陰離子、化學發光反應、吞噬率、吞噬指數皆明顯受到抑制，黑鯛血清中白蛋白-球蛋白比數值亦無顯著差異，但白蛋白、球蛋白數值則皆有下降的趨勢。

Abstract

The prupose of this study was investigated blood, muscle and liver tissue distribution in the black seabream (Acanthopagrus schlegelii) after a single injection of amoxicillin. And investigated the effect on non-specific immune parameters such as superoxide anion (O2-), chemiluminescent response, phagocytic rate, phagocytic indexs, albumin, globulin and albumin / globulin ratio (A/G ratio).
The result in experiment showed that the blood and liver tissues were found peak concentrations of amoxicillin occurring at 1 h after single injection (first sampling time) and amoxicillin residual concentrations decresed as time passed. The peak concentrations of blood and liver tissues were 82.53 μg/ml, 34.20 μg/g respectively. The amoxicillin residual concentrations in muscle tissues was added as time passed and peak concentrations of amoxicillin occurring at 4 h after single injection. The peak concentrations of muscle tissues was 2.99 μg/g. Then the amoxicillin residual concentrations in muscle tissues was decresed as time passed. Amoxicillin tissue concentrations decreased in the order blood, liver, muscle. The date conformed to a two-compartment model. The blood concentrations versus time curves were calculated using the biexponential equation : C = Ae-αt+Be-βt, get a biexponential equation : C = 94.15e-0.24t+8.76e-0.07t, k12=0.03,k21=0.08,kel =0.21 (h-1). According to pharmacokinetic parameters of amoxicillin in black seabream calculate that most amoxicillin were eliminate from central compartment,not distributed to the peripheral compartment. The result in experiment showed that the superoxide anion production, chemiluminescent response, phagocytic rate, phagocytic indexs were suppress by amoxicillin. The result also showed that albumin / globulin ratio were no significance, but the albumin and globulin level were decreased.

目錄
頁次
謝辭----------------------------------------------i
中文摘要------------------------------------------ii
英文摘要------------------------------------------iii
目錄----------------------------------------------v
表目錄--------------------------------------------vi
圖目錄--------------------------------------------viii
前言----------------------------------------------1
文獻整理-------------------------------------------3
材料方法------------------------------------------14
結果----------------------------------------------21
討論----------------------------------------------35
結論----------------------------------------------44
參考文獻------------------------------------------46
附錄----------------------------------------------71

參考文獻

朱德芬，1996。黑鯛人工養殖技術講座第一期，黑鯛生物學特性及增養殖概況，水產養殖。
行政院農業委員會令，2005。農授防字第0941472332號，動物用藥品使用準則。
巫文玲，1994。抗微生物-抗生素市場調查。經濟部產業技術資訊服務出版。
沈永紹，1991。獸醫實驗診斷學提要，第三版。華香園出版社。
沈亮廷，2003。飼料中不同蛋白質量與蛋白質與能量比對海鱺成長與體組成之影響。國立台灣海洋大學水產養殖學系碩士論文。
李健源，2000。比較不同定量法在Amikacin注射劑及Amoxicillin膠囊劑之生體可用率研究。中國醫藥學院藥物化學研究所碩士論文。
林欣穎，2002。裂褶菌多醣體的濃度分析及其對小白鼠之抗氧化活性 測試。國立臺灣大學動物學研究所碩士論文。
吳政翰，2004。β-葡聚多醣體對小白鼠吞噬細胞隻吞噬作用和細胞激素的影響：吞噬作用。國立台灣大學動物學研究所碩士論文。
邵廣昭，陳靜怡，2003。魚類圖鑑。遠流出版事業有限公司出版。pp.231。
施亞男，2004。葡聚多醣體與維他命C對海鱺非特異免疫反應的影響。國立台灣海洋大學水產養殖學系碩士論文。
胡王龍，劭慶均，王秀英，2004。池塘養殖黑鯛常見疾病的防治。中國水產第5期，51-52。
許清祥(總校閱)，2002。KUBY免疫學。合記出版社發行，7-8。
郭光雄，劉正義，劉朝鑫，1986。魚病專輯-鰻魚。抗生素緒論，61-72。
張德銘，黃勤業，林鉅鋃，2000。抗生素濫用影響國人健康專案調查報告。凱倫出版社。
陳悠里，2001。幾丁聚醣和衍生物對馬拉巴石斑魚免疫能力的影響。國立中山大學海洋生物研究所碩士論文。
陳秀男，2003。海鱺養殖技術研發與產業發展研討會會議資料輯。
陳巧玲，2005。葡聚多醣體與維他命C 對點帶石斑魚非特異免疫反應及生理之影響。國立海洋大學水產養殖系碩士論文。
楊聖信、林君穎、許桂森、張國志，1998。細菌細胞壁抑制劑。人體藥理學。藝軒圖書出版社，653-658。
劉朝鑫，1985。水產藥物之藥理及應用。漁業技術推廣，16。
劉振梅，1998。藥物化學-抗生素。中國科技醫藥出版社。
潘正安，1993。中華人民共和國藥典-藥典注釋,第二版二部1版，化學工業出版社。
蔡佳均，2006。不同濃度羥四環黴素對吳郭魚殘留量及非特異性免疫之影響。國立台灣海洋大學水產養殖學系碩士論文。
羅婉瑜，1999。腎上腺皮質醇與性類固醇激素對吳郭魚非特異性免疫之影響。國立台灣海洋大學水產養殖學系碩士論文。
蘇柏欣，2005。應用高效液相層析法檢測海鱺魚中amoxicillin的殘留。國立中興大學獸醫學系碩士論文。
Abedini, S., Namdari, R., Law, F.C.P., 1998. Comparative pharmacokinetics and bioavailability of oxytetracycline in rainbow trout and Chinook salmon. Aquaculture 162, 23-32
Acred, P., Hunter, PA., Mizen, L., Rolinson, GN., 1970. Amino-p-hydroxybenzylpenicillin (BRL 2333), a new broad- spectrum semisynthetic penicillin: in vivo evaluation. Antimicrobial Agents & Chemotherapy. 10:416-22.
Al-Ankari, A.S., Homeida, A.M., 1996. Effect of antibacterial growth promoters on the immune system of broiler chicks. Vet. Immuno Immunopathol. 53, 277-283.
Alderman, D.J., Michel, C., 1992. Chemotherapy in aquaculture tiday. In: C. Michel and D. Alderman（eds.), Chemotherapy in aquaculture:Form theory to reality. Office Internation Des Epizooties, Paris, France. 3-24.
Anderson, D.P., Zeeman, M.G., 1995. In Rand, G. M., Fundamentals of aquatic toxicology : Effects, environmental fate and risk asessment, 2nd eds. Taylors & Francis, Washington, D.C. Immunotoxicology in fish, pp. 371-404.
Ang, C.Y.W., Luo, W., Hansen, E.B., Freeman, J.P., Thompson, H.C., 1996. Determination of amoxicillin in catfish and salmon tissue by liquid chromatography with precolumn formaldehyde derivatization. J AOAC Int 79: 389-395.
Ang, C.Y.W., Luo, F.F., Lay, J.O., Luo, W., McKim, K., Gehring, T., Lochmann, R., 2000. Liquid chromatographic analysis of incurred amoxicillin residues in catfish muscle following oral administration of the drug. J. Agric. Food Chem 48, 1673-1677
Austin, B., 1985. Antibiotics pollution from fish farms：effects on aquatic microflora. Microbio. Sci. 2, 113-117.
Baggott, J.D., 1999. Farmacocinetica: cammino e destino dei farmaci nell’organismo. In: Adams, H.R. (Ed.), Farmacologia e terapeutica Veterinaria. EMSI, Roma, 29.
Balashev, V.N., Polosova, R.G., 1981. Experimental effect of tetracycline on the protein makeup of the lymph and blood serum. Antibiotiki 26(5), 374-8.
Bantar, C., Nicola, F., Canigia, L.F., Arenoso, H.J., Soutric, J., Montoto, M., Blanco, M., Smayersky, J., Jasorich, A., 2000. A pharmacodynamic model to support a 12-hour dosing interval for amoxicillin/sulbactam, a novel oral combination, in the treatment of community-acquired lower respiratory tract infections. J Chemother. 12, 223-7.
Black, W.D., Ferguson, H.W., Byrne, P., Claxton, M.J., 1991. Pharmacokinetic and tissue distribution study of oxytetracycline in rainbow trout following intravenous administration. J. Vet. Pharmacol. Ther. 14, 351– 358.
Brown, A.G., Grant, A.N., 1992. Use of amoxycillin by injection in Atlantic salmon broodstock.Vet. Rec. 131- 237.
Brown, A.G., Grant, A.N., 1993. Clinical efficacy of injectable amoxycillin against furuncolosis in Atlantic salmon broodstock. Vet. Rec. 133- 373.
Brusch, J.L., Bergeron, M.G., Barza, M., Weinstein, L., 1974. An in vitro and pharmacological comparison of amoxicillin and ampicillin. American Journal of the Medical Sciences. 267(1): 41-8.
Choudhury, D., Pal, A.K., Sahu, N.P., Kumar, S., Das, S.S., Mukherjee, S.C., 2005. Dietary yeast RNA supplementation reduces mortality by Aeromonas hydrophila in rohu (Labeo rohita L.) juveniles. Fish Shellfish Immunol. 19, 281-291.
Cole, M., Kenig, M.D., Hewitt, V.A., 1973. Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption. Antimicrobial Agents & Chemotherapy. 3(4): 463-8.
Coulibaly, K., Jeon, I.J., 1996. A overview of solid phase extraction of food flavor compounds and chemical residues. Food Review International. 12, 131-151.
Couso, N., Castro, R., Noya, M., Obach, A., Lamas, J., 2001. Location of Superoxide production sites in turbot neutrouphils and gilthead seabream acidophilic granulocytes during phagocytosis of glucan particles. Dev. Comp. Immunol. 25, 607-618.
Cox, C.E., 1974. Amoxicillin therapy of urinary tract infections. Journal of Infectious Diseases. 129(0): suppl:S235-6.
Croubels, S., Vanoosthuyze, K.I., Van Peteghem, C., 1997. Use of metal chelate affinity chromatography and membrane-based ion-exchange as clean-up procedure for trac residue analysis of tetracyclines in animal tissues and egg. J. Chromatogr B. 690, 173-17.
De Abreu, L.R.P., Ortiz, R.A.M., 2003. HPLC determination of amoxicillin comparative bioavailability in healthy volunteers after a single dose administration. J Pharm Pharmaceut Sci 6: 223-230.
Doumas, B.T., Watson, W.A., Biggs, H.G., 1971. Albumin standard and the measurement of serum albumin with bromcresol green. Clin. Chim. Acta. 31, 87-96.
Ellis, A.E., Roberts, R.J., Tytler, P., 1978. The anatomy and physiology of teleost. In: Roberts, R.J. (Ed.), Fish Physiology. Balliere Tindall, London, pp. 13–54.
Eshelman, F.N., Spyker, D.A., 1978. Pharmacokinetics of amoxicillin and ampicillin: crossover study of the effect of food. Antimicrobial Agents & Chemotherapy. 14(4), 539-43.
Fedeniuk, R.W., Shand, P.J., 1998. Theory and methodology of antibiotic extraction from biomatricrs. J. Chromatogr A. 812, 3-15.
Fernandez, N., Siera, M., Diez, M.J., Teran, T., Pereda, P., Garcia, J.J., 1997.Study of the pharmacokinetic interaction between ethinylestradiol and amoxicillin in rabbits. Contraception 55, 45-72.
Fletouris, D.J., Psomas, J.E., Botsoglou, N.A., 1990. Trace analysis of oxytetracycline and tetracycline in milk by high performance liquid chromatography. J. Agri. Food Chem. 38, 1913-1917.
Forsgren, A., Gnarpe, H., 1973. Tetracycline and host-defense mechanisms. Antimicrob. Agents. Chemother 3, 711-715.
Granham, S., Secombes, C.J. 1988. The production of a macrophage-activating factor from rainbow trout Salmo gairdeneri leucocytes. Immounol. 65, 293-297.
Grinde, B., 1989. A lysozyme isolated from rainbow trout acts on mastitis pathogens. FEMS Micro. Boil. Leet. 51, 179-182.
Grondel, J.L., Gloudemans, A.G.M., Muiswinkel, W.B.van., 1985. The influence of antibiotics on the immune system Ⅱ. Modulation of fish leukocyte responses in culture. Vet. Immunol. Immunopathol. 9, 251-260.
Grondel, J.L., Nouws, J.F.M., Muiswinkel van, W.B., 1987. The influence of antibiotics on the immunesystem:immune-pharmacokinetic investigations on the primary anti-SRBC response in carp(Cyprinus carpio L) after oxytetracycline injection. Journal of Fish Diseases 10, 35-43.
Grondel, J.L., Nouws, J.F., Schutte, A.R., Driessens, F., 1989. Comparative pharmacokinetics of oxytetracycline in rainbow trout (Salmo gairdneri) and African catfish (Clariasgarie pinus). J. Vet. Pharmacol. Ther. 12, 157-162.
Hand, W.L., Hand, D.L., King-Thompson, N.L., 1990. Antibiotic inhibition of the respiratory burst response in human polumorphonuclear leukocytes. Antimicrob. Agents Chemother. 5, 863– 870.
Harding, J.W. Lees, Lorna J. Amoxycillin, 1972. a new broad- spectrum penicillin(Amoxycillin) in general practice. Practitioner 209-363.
Heel, R.C., Speight, T.M., Avery, G.S., 1979. Amoxycillin injectable: a review of its antibacterial spectrum, pharmacokinetics and therapeutic use. [Review][74 refs] Drugs. 18(3):169-84.
Hoeben, D., Burvenich, C., Heyneman, R., 1998. Antibiotics commonly used to treat mastitis and respiratory burst of bovine polymorphonuclear leukocytes. J Dairy Sci 81, 403-410.
Inglis, V., Soliman, M.K., Ciapara, I.H., Richards, R.H., 1992. Amoxicillin in the control of furunculosis in Atlantic salmon parr. Vet. Rec. 130, 45- 48.
Inglis, V., Palmer, R., Shatwell, J.P., Branson, E.J., Richards, R.H., 1993. Amoxicillin concentrations in the serum of Atlantic salmon(Salmo salar L.)during furunculosis therapy. Vet. Rec. 133, 617- 621.
Jaime, N.D., William, A.R., 1995. Wilson and Gisvold's Textbook of organic Medicinal and Pharmaceutical Chemistry. J.B. Lippincott Company. Fourth Edition.
Jones, G.R., Calder, M.A., Froud, W.J., Inglis, J.M., Marr, F.M., Stewart, S.M., 1973. Amoxycillin: pilot study of its use in pneumonia and chronic bronchitis. British Journal of Clinical Practice. 27(5): 161-4.
Kim, K.H., Hwang, Y.J., Bai, S.C., 1999. Resistance to Vibrio alginolyticus in juvenile rockfish (Sebastes schlegeli) fed diets containing different doses of aloe. Aquaculture 180, 13-21.
Kiyota, K., Habu, Y., Sugano, Y., Inokuchi, H., Mizuno, S., Kimoto, K., Kawai, K., 1999. Comparison of 1-week and 2-week triple therapy with omeprazole,amoxicillin, and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial. Journal of Gastroenterology. 34 Suppl 11:76-9.
Lee, C.H., Paek, N.S., Kim, D.S., Kim, K.H., 2002. Effects of a Paecilomyces japonica-supplemented diet on the chemiluminescent response of phagocytes and growth in juvenile olive flounder (Paralichthys olivaceus). Aquaculture 208, 51-57.
Lunden, T., Miettinen, S., Lonnstrom, L.G., Lilius, E.M., Bylund, G., 1998. Influence of oxytetracycline and oxolinic acid on the immune response of rainbow trout (Oncorhynchus mykiss). Fish & Shellfish Immunology 8, 217-230.
Lunden, T., Miettinen, S., Lonnstrom, L.G., Lilius, E.M., Bylund, G., 1999. Effect of florfenicol on the immune response of rainbow trout (Oncorhynchus mykiss). Vet. Immuno Immunopathol. 67, 317-325.
Lunden, T., Lilius, E.M., Bylund, G., 2002. Respiratory burst activity of rainbow trout (Oncorhynchus mykiss) phagocytes is modulated by antimicrobial drugs. Aquaculture 207, 203-212.
MacNeil, J.D., Marze, V.K., Korsrud, G.O., Craic, D.C., 1996. Chlortetracycline, oxytetracycline, tetracycline in edible animal tissues, liquid chromatography method: collaborative study. J. Assoc. Off. Anal. Chem. 79, 405-417.
Martinsen, B., Horsberg, T.E., Varma, K.J., Sams, R., 1993. Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11°C. Aquaculture 112, 1-11.
Martinsen, B., Horsberg, T.E., 1995. Comparative single-dose pharmacokinetics of four quinolones, oxolinic acid, flumequine, sarafloxacin and enrofloxacin in Atlantic salmon (Salmo salar) held in seawater at 10 °C. Antimicrob. Agents Chemother. 39, 1059-1064.
Mazzolini, E., Vismara, D., Ceschia, G., Malvisi, J., Fabris, A., Passera, A., Danielis, L., Giorgetti, G., 1997.‘‘In vitro’’ activity of several antibiotics against clinical isolated of marine fish pathogens. Int. Workshop: ‘‘Aquaculture Application of Controlled Drug and Vaccine Delivery’’, 21- 23 May, Villa Manin di Passariano (UD).
Miki, F., 1973. Absorption, excretion, distribution and distribution and metabolism of amoxycillin. Paper present at an International Symposium on amoxycillin,London, September.p.25.
Moats, W.A., 1986. Determination of tetracycline antibiotics in tissues and blood serum of cattle and swine by high performance liquid chromatography. J. Pharam. Biol. Analysis. 358, 253-259.
Nakauchi, R., Wakabayashi, T., Yasunaga, N., Tukahara, J., Kimura, M., Kubota, S.S., 1989. Therapeutic effect of amoxicillin against pseudoberculosis in yellowtail, Seriola quinqueradiata. Bull. Nippon Vet. Zootech. Coll. 38, 72-78.
Namdari, R., Abedini, S., Albright, L., Law, F.C.P., 1998. Tissue distribution and elimination of oxytetracycline in sea pen cultured chinook salmon Oncorhynchus tshawytscha and Atlantic salmon (Salmon salar L.) following medicated feed treatment. J. Appl. Aquacult. 8, 39– 52.
Pankey, G.A., 1974. Clinical experience with amoxicillin in the treatment of skin infections. Journal of Infectious Diseases. 129(0):suppl: S202-6.
Pieramico, O., Zanetti, M.V., Innerhofer, M., Malfertheiner, P., 1997. Omeprazole-based dual and triple therapy for the treatment of Helicobacter pylori infection in peptic ulcer disease: a randomized trial. Helicobacter. 2(2):92-7.
Plakas, S.M., McPearson, R.M., Guarino, A.M., 1988. Disposition and bioavailability of 3H-tetracycline in the channel catfish (Ictalurus punctatus). Xenobiotica 18, 83– 93.
Plakas, S.M., El said, K.R., Musser, S.M., 2000. Pharmacokinetics, tissue distribution, and metabolism of flumequine in channel catfish (Ictalurus punctatus). Aquaculture 187, 1-14.
Rigos, G., Alexis, M., Andriopoulou, A., Nengas, I., 2002. Pharmacokinetics and tissue distribution of oxytetracycline in sea bass (Dicentrarchus labrax) at two water temperatures. Aquaculture 210, 59- 67.
Rigos, G., Nengas, I., Tyrpenou, A.E., Alexis, M., Troisi, G.M., 2003. Pharmacokinetics and bioavailability of oxytetracycline in gilthead sea bream (Sparus aurata) after a single dose. Aquaculture 221, 75-83.
Rocca, G.D., Zaghini, A., Zanoni, R., Sanguinetti, V., Zanchetta, S., Salvo, A.D., Malvisi, J., 2004. Seabream (Sparus aurata L.): disposition of amoxicillin after single intravenous or oral administration and multiple dose depletion studies. Aquaculture 232, 1-10.
Rogstad, A., Hormazabal, V., Yndestad, M., 1988. Optimization of solid phase extraction of oxytetracycline from fish tissue and its determination by HPLC. J. Liq. Chromatogr. 11, 2337-2347.
Sabto, J., Carson, P., Morgan, T., 1973. Evaluation of amoxycillin--a new semisynthetic penicillin. Medical Journal of Australia. 2(11): 537-41.
Sahoo, P.K., Mukherjee, S.C., 2001. Effect of dietary β-1,3 glucan on B1-induced immunocompromised rohu (Labeo rohita Hamilton).Fish Shellfish Immunol. 11, 683-695.
Samuelsen, O.B., Ervik, A., 1997. Single dose pharrnacokinetic study of flumequine after intravenous, intraperitoneal and oral administration to Atlantic halibut (Hippoglossus hippoglossus) held in seawater at 9°C. Aquaculture 158, 215-227.
Santarem, M., Figueras, A., 1995. Leucocyte numbers and phagocytic activity in turbot Scophthalmus maximus following immunization with Vibrio damsela and Pasteurella piscicida o-antigen bacterins. Dis. Aquat. Org.23. 213-220.
Shojaee, AliAbdabi, F., Lees, P., 2000. Antibiotic treatment for animals: effect on bacterial population and dosage regimen optimisation. Int. J. Antimicrob. Agents 14, 307-313.
Siwicki, A.K., Anderson, D.P., Dixon, O.W., 1989. Comparisons of nonspecific and specific immunomodulation by oxolinic acid, oxytetracycline and levamisole in salmonids. Vet. Immunol. Immunopathol. 23, 195- 200.
Siwicki, A.K., Anderson, D.P., Rumsey, G.L., 1994. Dietary intake of immunostimulants by rainbow trout affects non-specific immunity and protection against furunculosis. Vet. Immunol. Immunopathol. 41, 125-139.
Song, Y.L., Hsieh, Y.T. 1994. Immunostimulation og tiger shrimp (Penaeus monodon) hemocytes for generation of microbicidal substances: Analysis of reactive oxygen species. Dev. Comp. Immunol. 18, 201-209.
Spyker, D.A., Rugloski, R.J., Vann, R.L., O’Brien, W.M., 1977. Pharmacokinetics of amoxicillin: Dose dependence after intravenous, oral, and intramuscular administration. Antimicrobial agents and chemotherapy, Jan. 1977, p. 132-141
Stubbings, G., Tarbin, J.A., Shearer, G. 1996. On-line metal chelate affinity chromatographic determination of sulfamethazine and sulfathiazole in feeds and feed premixes. J. Assoc. Off. Anal. Chem. 65.823-827.
Tukahara, J., Yasunaga, N., Nakauchi, R., Nakayama, H., Hatai, K., Kubota, S.S., 1989. Absorption, distribution and excretion of amoxycillin in yellowtail. Bull. Nippon Vet. Zootech. Coll. 38, 66- 71.
Uno, K., 1996. Pharmacokinetic study of oxytetracycline in healthy and vibriosis-infected ayu (Plecoglossus altivelis). Aquaculture 143, 33-42.
Uno, K., Aoki, T., Ueno, R., Maeda, I., 1997. Pharmacokinetics and metabolism of sulphamonomethoxine in rainbow trout (Oncorhynchus mykiss) and yellowtail (Seriola quinqueradiata) following bolus intravascular administration. Aquaculture 153, 1-8.
Vaden, S.L., Riviere, J.E., 1995. Penicillin and related β-lactams antibiotics. In: Adams, H.R. (Ed.), Veterinary Pharmacology and Therapeutics, 7th ed. IOWA State Univ. Press, p. 778. Chapter 40.
Van der Heijden, M.H.T., Keukens, H.J., van den Nieuwboer, W.H.F.X., Mengelers, M.J.B., Boon, J.H., 1994. Plasma disposition of flumequine in common carp (Cyprinus carpio L., 1758), African catfish (Clarias gariepinus Burchell, 1822) and European eel (Anguilla anguilla L., 1758) after a single per oral administration. Aquaculture 123, 21-30.
Walsh, J.R., Walker, L.V., Webber, J.J., 1992. Determination of tetracycline in bovine and porcine muscle by high-performance chromatography using solid-phase extraction. J. Chromatogr. 596, 211-216.
Weichselbaum, T.E., 1946. An accurate and rapid method for the determination of proteins in small amounts of blood serum and plasma. Am. J. Clin. Pathol. 16, 40-49.
Welling, P.G., Huang, H., Koch, P.A., Craig, W.A., Madsen, P.O., 1977. Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects. Journal of Pharmaceutical Sciences. 66(4):549-52.
Westphal, J.F., Deslandes, A., Brogard, J.M., Carbon, C., 1991. Reappraisal of amoxycillin absorption kinetics. Journal of Antimicrobial Chemotherapy. 27(5):647-54.
Wingard. Brody. Larner. Schwartz. 1991. Human pharmaco-logy, Mosby-Year Book.
Yaffe, S.J., Aranda, J.V., 1992. Pediatric pharmacology: therapeutic principles in practice. W.B. Saunders, Philadelphia, USA, 237-243.