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研究生:林庭攸
研究生(外文):lin ting yu
論文名稱:雪華立新於雞之殘留停藥期試驗
論文名稱(外文):Residual Level and Withdrawing Time Determination of Cephalexin in Chicken
指導教授:呂車鳳劉宏仁劉宏仁引用關係
學位類別:碩士
校院名稱:國立屏東科技大學
系所名稱:獸醫學系
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:69
中文關鍵詞:雪華立新殘留停藥期試驗
外文關鍵詞:CephalexinResidual LevelWithdrawing Time
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中文摘要
本試驗旨在探討Cephalexin monohydrate於國內飼養環境下雞之適宜口服劑量及其殘留停藥期。首先由不同場的病雞所分離之Staphylococcus spp. (10株)、E.coli (13株) 及Salmonella spp. (4株)進行cephalexin試管中的最小抑制濃度(MIC)值之測定。試驗結果得到MIC90為16 ppm。故決定以MIC90值之3倍(即48 mg/kg,BW)劑量強迫口服投藥(每單一雞隻口服0.4 mL)一次/天,投予隻數為24隻(平均體重700克/隻)。於投藥後0.5、1、2、4、6、8、10及12小時,各時段分別採集三隻雞的血液,分離血清,並進行血中藥物的評估。試驗結果顯示:48 mg/kg劑量於停藥後0.5小時達到血中最高濃度( 19.51 ppm );1小時後降至血中半量( 為9.08 ppm );6小時後尚有少量殘留( 約 < 0.025 ppm );到8小時後血中已無任何藥品殘留。經此試驗,發現cephalexin於雞體內排泄速率快(半衰期短)無法達到有效的血中濃度。故決定採用cephalexin 350 ppm之劑量,飲水投予(任食)雞隻一天,並於投藥開始起2、4、6、8、10、12、14、16、18、20、22、24小時採血,分離血清,進行藥物濃度評估。結果顯示:仍無法達到有效血中濃度(血中濃度最高0.79 ppm )。最後決定以5000 ppm 飲水投予(任食)一天,並於投藥開始起2、4、6、8、10、12、14、16、18、20、22、24小時等時段各採三隻雞隻血液,分離血清,進行藥物濃度評估。結果發現,可以達到相當於MIC90的有效血中濃度;而且雞隻在臨床上並無不適現象出現,且其血清生化值AST等及組織病理切片檢查亦無顯著性變化。因此推定,cephalexin的安全有效飲水口服劑量為5000 ppm。Cephalexin 5000 ppm (相當於600 mg/kg B.W./day)以飲水添加任食方式進行,連續三天。並於停藥後0、4、8、12、16、20、24小時及2、3、4、5、6、7、8、9、10、11、12、13、14天等各時段各宰殺3隻雞,採集血清、肝、腎、肌肉以HPLC進行殘留分析。依分析結果:血清在停藥後8小時,肝於第九天、腎在第八天起就檢測不到(即低於0.25 ppm);肌肉中於第16小時有5.9 ppm殘留,第十天起即檢測不到( 即低於0.25 ppm )。故cephalexin以 5000 ppm 飲水中投予連續投與三天後,於雞之停藥期宜為15天。
Abstract
This study attempts to determine not only an appropriate dosage of
cephalexin monhydrate, but also the cephalexin monohydrate residue in chicken under the Taiwan`s normal raising condition. The in vitro anti-bacterial activity of cephalexin against 3 varieties of clinical bacterial isolates of a total of a total 27 strains from chicken were evaluated.The drug inhibits more than 90% of the strains (MIC90) at a concentration of 16 ppm. So the dosage of 48 mg / kg BW / daily ( equivalent to 3 times of MIC90 value) of cephalexin monohydrates were first selected and ad-ministered orally ( 0.4mL solution / chicken ) to 24 chickens ( 700 g BW / chicken ) .Three chicken`s sera were collected for determination of the drug concentration at time intervals of 0.5,1,2,4,6,8,10 and 12 hours after administration of the drug. Experimental results indicate that the peak serum concentration of cephalexin monohydrate that appeared 0.5 hours after the drug administered was 19.51 ppm , then it decreased to 9.08ppm at 1 hour interval, and 0.025 at 6 hours thereafter,it could’nt be detected at the interval of 8 hours any more .
According to the results,it was found that cephalexin was ex-crected too fast ( with short half life ) to reach an effective blood concen-tration. Therefore a larger dosage of 350 ppm of cephalexin in drinking water to chicken for one day were employed. The chicken sera were col-lected and for determination of their cephalexin concentrations at the time intervals of 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 hours after taking the drug orally .The results show that it also could’nt reach an efective blood concentrations (with a peak concentration of 0.79ppm).Therefore , the dosage of cephalexin in drinking water was increased to 5000 ppm for 24 hours . The samples sera were then monitored at the time intervals of 4,8,12,16,20 and 24 hours after the drug was administered.
As a result , the dosage of 5000 ppm reached to an effective blood concentration(over the MIC90) and chickens didn’t show any clini-cally uncomfortable phenomena , nor significant change by utilizing sera biochemical and pathological investigations.Therefore the appropriate dosage of cephalexin in drinking water for chicken was decided to be 5000 ppm, which is equivalent to 600 mg /kgBW /daily.And it was ad-ministered to chichens for 3 consecutive days.Three chickens were acu-punctured and anatomised at each time interval of 0, 4, 8, 12, 16, 20, 24 hours for the first day and after that, three chicken each day for two weeks.After withdrawing the drug,and samples of sera,liver,kidney,meat were collected for high perfermance liquid chromatography analy-sis.According to the analytical results,chicken meat appeared a residue level of 5.9 ppm at 16 hours.The cephalexin in chicken sera,liver and kidney was too low to be detected (below 0.25ppm) at 8 hours, 9days and 8 days after withdrawing the drug respectively . Our results further demonstrate that the best withdrawal time for cephalexin monohydrate via oral administration in chicken is 15 days.
目 錄
頁 次
中文摘要………………………………………1
英文摘要………………………………………3
誌  謝………………………………………5
第一章 緒  言……………………………11
第二章 文獻探討……………………………15
第三章 材料與方法…………………………34
第四章 結  果……………………………56
第五章 討  論……………………………60
第六章 參考文獻..…………………………62
六、參考文獻
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