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標題: 四環黴素及磺胺甲基噁唑在水耕小白菜的藥物動力學:吸收、分布、代謝及排除
The pharmacokinetics of tetracycline and sulfamethoxazole in Brassica chinensis L. grown under hydroponic conditions: the uptake, distribution, metabolism and elimination
作者: 吳郁潔
Wu, Yu-Jie
關鍵字: 四環黴素;pharmacokinetics;磺胺甲基噁唑;小白菜;藥物動力學;tetracycline;sulfamethoxazole
出版社: 獸醫學系暨研究所
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四環黴素(Tetracycline, TC)和磺胺劑類(Sulfamethoxazole, SMX)為廣泛用於飼料及獸醫治療用途的抗生素類,這些抗生素有高達70 %可以原型或代謝產物形式經由尿液或糞便排出。近年來各國廣泛於土壤及廢水中檢測出μg/mL等級的抗生素濃度,導致環境中的抗生素有可能經由食用植物逆向返回食物鏈或人體的可能性逐漸受到重視。然而,目前抗生素類在植物的藥物動力學(吸收、分佈、代謝及排除)相關研究並不多,有關藥物在植物殘留的資訊亦相對匱乏。因此,本研究擬以水耕小白菜食用植物建立抗生素的完整藥物動力學模式,了解這2類抗生素在蔬菜的移動行為。實驗使用鳳京(Tokita)品種之水耕小白菜,種植於含100 μg/mL TC(或SMX)抗生素之水耕液中共100 mL。以既定間隔採集小白菜之根、莖、葉及培養液測其藥物濃度。樣品經萃取後以HPLC-UV進行偵測。TC及SMX之偵測極限分別為100 ng/mL及50 ng/mL。結果指出,小白菜中TC在根內濃度最高,葉中次之,而莖中最低。且根的濃度在第24小時高達1200 μg/mL且有累積的現象(BAF=21)。TC在葉的濃度在50-60 μg/mL之間,在莖則是10-20 μg/mL。SMX在小白菜各部位的濃度亦為根中濃度最高,莖和葉次之,濃度分別約為30、10和7 μg/mL之間,BAF在根為0.4,莖和葉皆為0.1。三種不同濃度(100、10和1 μg/mL)下比較發現兩種抗生素的吸收和分佈非常相似,證明現在的model也合適用於環境中低濃度抗生素殘留的實況。兩種抗生素在同株每片莖之間和每片葉之間的濃度並沒有顯著差異。在給予TC五天後以HPLC及質譜分析,皆可於葉部發現TC生轉化為Doxycycline,而在給予SMX的組別則在小白菜任何部位皆未檢測到可能的代謝產物。將已經吸收藥物的小白菜,放回到清水中以了解蔬菜排除藥物的能力,結果顯示TC和SMX的排除主要發生在前30分鐘,濃度下降在15~30 %之間,隨後濃度則維持在一穩定狀態。綜合以上結論,TC和SMX在小白菜的藥物動力學表現有著明顯的差異,小白菜吸收TC之能力遠大於吸收SMX,平均每克的菜可以吸收200 μg的TC和6.2 μg的SMX,且極可能具有代謝這些藥物的能力,釋放時則似乎有一個控制的機制或者藥物一旦與蔬菜結合,即不容易脫離。未來,應進一步探討TC和SMX在土耕小白菜的藥物動力學。

Veterinary antibiotics are increasingly being monitored in slurry, soils and surface waters as ground waters have been reported to have antibiotic concentrations ranging from several to hundreds of milligrams per liter. The most commonly detected antibiotics in soil and river in Taiwan are sulfonamides, tetracyclines and lincosamides, the concentrations range between 1570 to 111667 ng/L. Therefore, antibiotics uptake by plants in soil and water matrix becomes not only an environmental but also a human health concern. Our aims are to investigate the pharmacokinetic behaviors (uptake, distribution, metabolism and elimination) of tetracycline (TC) and sulfamethoxazole (SMX) in edible vegetable Brassica Chinensis L.. The vegetable was exposed to 100 μg/mL TC or SMX in cultivation water for up to 24 hrs, drug concentrations in roots, stems and leaves were quantified using optimized HPLC-UV method and the bioaccumulation factors (BAF) in various parts of the vegetable were calculated. The results showed evident differential uptake and distribution of the two antibiotics. TC concentration in the root was as high as 1200 μg/mL, indicating accumulation of the drug in the root (BAF=21 at 24 hr). TC concentration in the leaves was around 50-60 μg/mL while only 10-20 μg/mL was detected in the stem. SMX concentrations in the root and stem/leaves were approximately 30 and 10 μg/mL, respectively, representing BAFs of 0.3 and 0.1. The percentage uptake of TC and SMX by the vegetable were similar at 3 concentration levels (100, 10 and 1 μg/mL) indicating the appropriateness of the current model and the ability of Brassica Chinensis L. to uptake high amount of TC. TC was biotransformed to doxycycline in the leaves on day 5 after exposure while SMX was not metabolized to significant degree. Elimination of TC and SMX from the vegetable back into the cultivation water was noted mainly in the first 0.5 hrs (20-30% reduction) before it reached equilibrium. In conclusion, the pharmacokinetic behaviors of TC and SMX varies in Brassica Chinensis L., it could be significantly uptaken to different parts of the vegetable, being metabolized to different degree and released back to the environment through the root in a controlled manner.
其他識別: U0005-3008201312404300
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