| Summary: | 博士 === 國立中興大學 === 獸醫學系暨研究所 === 107 === Tetracyclines (TCs) and sulfonamides (SAs) are common applications as food-additives and therapeutic treatment in veterinary medicine. In recent years, antibiotic residues are increasingly being monitored in slurry, soils and surface waters as ground waters have been reported to have concentrations ranging from micrograms to milligrams per liter in many countries. To the best of our knowledge, very few studies have examined the fate of antibiotics in the edible plants other than to study their accumulations and none of them was studied from the pharmacokinetic perspectives, which includes the adsorption, distribution, metabolism and elimination. Therefore, the main purposes of the study were focused on two popular vegetables in Taiwan and to demonstrate the novel use of pharmacokinetic approaches to study the movements of antibiotics in edible plants. Brassica rapa Chinensis and Ipomoea aquatic were grown in cultivation fluids containing 100 µg mL-1 TC or SMX for 24 hours and drug concentrations were analyzed by HPLC with LC-MS-MS detection. The absorption results indicated that ephemeral vegetables could have high capacity accumulating antibiotics within hours (up to 160 µg g-1 for TC and 18 µg g-1 for SMX in B. rapa Chinensis and 77 µg g-1 for TC and 38 µg g-1 for SMX in I. aquatica). TC concentration in the root of B. rapa Chinensis (Cmax) could reach 21 times higher than that in the cultivation fluid and concentration in the leave reach 1.2 times higher than in the cultivation fluid, but there were no bioaccumulation for TC and SMX in I. aquatica . For elimination, B. rapa Chinensis could release 11% (TC) and 8% (SMX) of the drugs back into the cultivation fluid while in I. aquatica they were released 25% (TC) and 28% (SMX) for 24 hours. Non-compartmental analysis indicated that TC and SMX exhibited distinct PK behaviors in vegetables grown hydroponically. Cmax of TC could reach as high as 1124 µg mL-1 which was over 34 folds more than SMX concentration in the roots of B. rapa Chinensis and more than 32 folds and 182 folds of TC and SMX in the root of I. aquati. Based on the volume of distribution (Vd), SMX was 3-6 times more extensively distributed than TC. Both antibiotics showed slow albeit evident elimination phases with elimination half-lives ranging from 22 to 88 hours. When vegetables were exposed to 100 μg mL-1 TC or SMX in soil for 21 days, the detectable levels of either drug were very low in both vegetables (below 10 μg mL-1). Possible reasons are likely associated with the degradation of drugs and the complexity of rhizosphere (soil characters, microorganism, pH, ion strengths, and humidity) that hindered the drug absorption. In the field investigations of a total of 335 samples (vegetables 265 and weeds 70) on the levels of TCs and SMX near pig farms or from traditional market in Taiwan, results showed that 28% of vegetables and 64% of weeds near pig farms contained at least one TCs. The detection rate of vegetables was twice higher near the pig farm than in the traditional market. OTC(20%) and CTC(33%) were most commonly detected while the detection rate was very low in SMX. DC level could reach as high as 231 ng g-1 in Chinese cabbage and OTC level 746 ng g-1 in nut grass among all plants. The soils and the discharges water near the pig farms also showed very high contamination rate (87% and 100%) of these two drugs. We have demonstrated for the first time that pharmacokinetics approaches commonly used in animal model could be used to at least partially describe drug behaviors in the plants. Phyto-pharmacokinetics could be a new area worth development of new models for risk assessment of veterinary drugs.
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