임신가토에 있어 Oxytetracycline의 흡수와 배설에 관한 연구

김현중(HJ Kim),이철진(CJ Lee),문호길(HG Moon),임광호(KH Lim) 대한산부인과학회 1982 Obstetrics & Gynecology Science Vol.25 No.1

약물의 생체내 이용 효율에 관한 연구로 Oxytetracycline의 흡수와 배설을 매시간당 6회에 걸쳐 측정하여 임신가토, 비임신 가토 및 웅성 가토와 비교 관찰하였다. 1. 임신 초기 자성, 가토군, 임신말기 자성 가토군, 비임신 자성 가토군 및 웅성 가토군에서 흡수된 Oxytetracycline의 혈중 농도는 2시간째에 최고농도에 이르게 되는데, 이때의 혈중농도는 각각 28.0 mcg/ml, 24.0 mcg/ml, 33.0 mcg/ml 및 30.0 mcg/ml이다. 2. 임신 초기 자성 가토군, 임신말기 자성 가토군, 비임신 자성 가토군 및 웅성 가토군에서 흡수된 Oxytetracycline의 뇨 배설량은 역시 2시간째에 최고에 달하게 되는데 이때의 측정치는 각각 31.36 mcg/min, 26.64 mcg/min, 37.95 mch/min, 34.50mcg/min이다. 3. Oxytetracycline의 뇨중 청소율은 각군에서 1.04 ml/min내지 1.05 ml/min로서 별 변동이 없었다. The absorption and excretion of oxytetracycline in pregnant rabbit for drug availability were measured hourly at 6 times to compare with them in non-pregnant rabbit group and male rabbit group. 1) The blood levels of oxytetracycline in early pregnant rabbit group, late pregnant rabbit group, non-pregnant rabbit group and male rabbit group were respectively 28, mcg/ml, 24.0mcg/ml, 33.0mcg/ml and 30.0 mcg/ml at the second hour, which they were in peak. 2) The excretion of oxytetracycline in early pregnant rabbit group, late pregnant rabbit group, non-pregnant rabbit group and male rabbit group were respectively 31.36mcg/min, 26.64mcg/min, 37.95 mcg/min and 34.50 mcg/min at the second hour, which they were in peak. 3) The urinary clearance rates of oxytetracycline in blood were evenly unchangable in each groups in the range from 1.04 ml/min to 1.15 ml/min.

하천에서의 Oxytetracycline 내성주에 관한 연구

김영진,김종오,Kim, Young Jin,Kim, Jong Oh 한국환경보건학회 2015 한국환경보건학회지 Vol.41 No.1

Objectives: This study aims to understand the concentration, diversity, and antibiotic characteristics of oxytetracycline resistant bacteria present in a surface water environment. Methods: Water sampling was performed in Cheongmi Stream in Gyeonggi-do, Korea in February and August 2014. Water samples collected from two sites were plated in triplicate on tryptic soy agar plates with 30 mg/L of oxytetracycline. Oxytetracycline resistant bacteria were selected from surface water in Cheongmi Stream and were subjected to 16S rDNA analysis for oxytetracycline resistant species determination. Identified resistant strains were tested for resistance to various antibiotics. Results: Results from this study indicate that the dominant resistant organisms in this aquatic environment are from family Acinetobacter and family Aeromonas. As to culturable heterotrophic bacteria, Oxytetracycline resistant bacteria were present 0.45-0.93% during winter and 0.08-0.38% during summer. Most oxytetracycline resistant bacteria exhibited resistance to more than ten of the antibiotics studied. The diversity of oxytetracycline resistant bacteria in winter was higher than in summer. Conclusion: Most of these resistant bacteria are Gram negative and are closely related to pathogenic species. These results suggest that increasing multi-antibiotic resistant bacteria in the surface water environment has a close relation to the reckless use of antibiotics in livestock.

Degradation of Oxytetracycline by Persulfate Activation Using Hand Warmer Waste

Eun Hea JHO,Youn Jun LEE,Chang-gu LEE 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Reactive radical species are widely used for the removal of organic compounds in wastewater. These species are usually generated by activating peroxides (eg., hydrogen peroxide, persulfate, peroxymonosulfate) using catalysts. Among various catalysts, iron-based catalysts such as ferrous, ferric, and iron oxide are widely used for the activation of peroxide because it is effective and less expensive. In this study, waste of hand warmer was magnetically separated and was used as a persulfate activator for the removal of antibiotics, oxytetracycline. The degradation of oxytetracycline in the presence of catalyst and persulfate was studied by analyzing residual concentration of oxytetracycline in the samples. The removal ratio of oxytetracycline by persulfate activation was more than 99% for 5 min of reaction time at pH 6. In addition, the reuse test revealed that the catalyst can be reused for 8 cycles. The results suggest that the hand warmer waste can be an efficient catalyst for persulfate activation.

QuEChERS법 및 LC-MS/MS를 이용한 농산물 중 Oxytetracycline의 잔류시험법 개발 및 검증

조성민,도정아,이한솔,박지수,신혜선,장동은,조명식,정용현,이강봉 한국식품위생안전성학회 2019 한국식품위생안전성학회지 Vol.34 No.3

An analytical method was developed for the determination of oxytetracycline in agricultural products using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After the samples were extracted with methanol, the extracts were adjusted to pH 4 by formic acid and sodium chloride was added to remove water. Dispersive solid phase extraction (d-SPE) cleanup was carried out using MgSO 4 (anhydrous magnesium sulfate), PSA (primary secondary amine), C 18 (octadecyl) and GCB (graphitized carbon black). The analytes were quantified and confirmed with LC-MS/MS using ESI (electrospray ionization) in positive ion MRM (multiple reaction monitoring) mode. The matrix-matched calibration curves were constructed using six levels (0.001~0.25 μg/mL) and coefficient of determination (r2 ) was above 0.99. Recovery results at three concentrations (LOQ, 10×LOQ, and 50×LOQ, n=5) were from 80.0 to 108.2% with relative standard deviations (RSDs) less than of 11.4%. For inter-laboratory validation, the average recovery was in the range of 83.5~103.2% and the coefficient of variation (CV) was below 14.1%. All results satisfied the criteria ranges requested in the Codex guidelines (CAC/GL 40-1993, 2003) and the Food Safety Evaluation Department guidelines (2016). The proposed analytical method was accurate, effective and sensitive for oxytetracycline determination in agricultural commodities. This study could be useful for safety management of oxytetracycline residues in agricultural products.

Oxytetracycline과 neomycin 복합제의 약욕에 따른 양식 넙치(Paralichthys olivaceus)의 근육내 잔류량 변화

김승민,전려진,정준범,Kim, Seung Min,Jun, Lyu Jin,Jeong, Joon Bum 한국어병학회 2015 한국어병학회지 Vol.28 No.1

본 연구에서는 넙치 (평균체장 및 무게: $20{\pm}2.0cm$, $70{\pm}5.0g$)에 옥시테트라사이클린(oxytetracycline, OTC)-네오마이신(neomycin, N) 복합제를 25-10 ppm 및 50-20 ppm으로 용해하여 2일 동안, 3시간씩 약욕을 실시하였고, 약물투여 중지 후 1일, 5일, 14일, 40일째에 시험군별로 각각 5마리씩 넙치의 근육을 채취하여 항생제 잔류농도를 조사하였다. OTC와 N 표준용액을 농도별로 희석하여 표준곡선을 작성한 결과 각각 $R^2=0.9999$, $R^2=0.9952$로 양호한 직선성을 나타내었고, OTC와 N 회수율은 각각 90~93%, 88~95%가 관찰되었다. 잔류농도에 대한 측정결과, OTC와 N 복합제를 25-10 ppm 투여한 시험군에서 1일째 OTC는 $0.97{\pm}0.084{\mu}g/ml$이 검출되었고, N은 $0.118{\pm}0.079{\mu}g/ml$이 검출되었으나 5일째 이후부터 검출이 되지 않았다. OTC와 N 복합제를 50-20 ppm 투여한 시험군에서 1일째 OTC는 $1.324{\pm}0.062{\mu}g/ml$이 검출되었고 N은 $0.788{\pm}0.05{\mu}g/ml$이 검출되었으나 5일째 이후부터 검출이 되지 않았다. In the present study, we performed a dipping of olive flounder (average length and weight: $20{\pm}2.0cm$, $70{\pm}5.0g$) for a period of three hours a day, over two days, in a melted complex of oxytetracycline (OTC) and neomycin (N), by dissolving 25-10 ppm or 50-20 ppm in water. Subsequently, the remaining antibiotic density in muscle tissue collected from olive flounder was investigated, 1, 5, 14 and 40 days after discontinuation of the medication. 5 fish were used from each group. The standard graph drawn from the results of diluting two standard solutions of OTC and N based on various density levels, showed a relatively straight line with an $R^2$ of 0.9999 and 0.9952, respectively. The recovery rate of OTC was shown to be 90-93% and N, 88-95%. Upon measurement of the remaining antibiotic density in the test group that had been exposed to 25-10 ppm of the complex of OTC and N, $0.97{\pm}0.084{\mu}g/ml$ of OTC and $0.118{\pm}0.079{\mu}g/ml$ N were detected on 1 day of the test. No antibiotic density was detected after day 5 of the test. Regarding the test group that were exposed to 50-20 ppm of the complex of OTC and N, $1.324{\pm}0.062{\mu}g/ml$ of OTC and $0.788{\pm}0.05{\mu}g/ml$ N were detected on day 1 of the test, and no antibiotic density was detected after day 5 of the test.

Oxytetracycline의 투여방법에 따른 넙치(Paralichthys olivaceus) 체내의 잔류 특성

고창식(Chang-Sik Ko),김동휘(Dong-Hwi Kim),박소현(So-Hyun Park),문경미(Kyung-Mi Moon),허문수(Moon-Soo Heo) 한국생명과학회 2016 생명과학회지 Vol.26 No.3

어류 질병은 매년 대규모 해산물 양식 및 소비량에 따라 증가하고 있으며, 이를 예방 및 치료하기 위해 항생제인 OTC (Oxytetracycline)를 사용하고 있다. 하지만 이는 부적절한 사용 및 오남용을 하게 되면 인체 내 통증을 유발시킬 수 있다고 알려져 있다. 따라서 본 연구에서는 간이시험법 및 HPLC 분석과 함께 OTC의 약욕 처리 및 경구 투여에 따른 넙치의 피부, 간, 근육에 관해 연구하였다. 약욕처리구는 물 1톤당 25 g의 농도로 1시간 1회 실시 하였고, OTC의 투여 농도를 어체중 ㎏ 당 62.5 ㎎을 사료에 혼합시켜 7일간 경구 투여하였다. 미생물학적간이 검사법에서 약욕 처리구는 피부 직후에서만 양성을 보였고 경구 투여구에서는 77일째 양성으로 조사되었다. 그리고 근육은 14일째까지 양성을 보였다. HPLC 분석에서는 약욕 처리구인 간에서는 13일째, 피부는 37일째 잔해가 남은 것을 확인할 수 있었고 근육에서는 발견하지 못했다. 경구 투여구인 피부에서는 높은 농도(1.07 ㎎/㎏)로 나타났으며, 간에서는 소량(0.56 ㎎/㎏)을 나타냈으며 42일째의 근육에서는 남아 있지 않았다. 종합적으로 어류 양식장에서 사용 되는 OTC의 휴약 기간을 40일로 준수하면 OTC는 거의 잔류하지 않고 우리 몸에 무해하나 영양물질의 중간대사 또는 저장, 해독 등의 중요한 역할을 하는 간과 어체의 몸의 표면을 보호하고 감각작용을 하는 역할을 하는 피부는 근육에 남아 있는 OTC의 잔류량보다 몇 배의 높은 수치를 나타냈다. 하지만 이는 이전 연구에 따르면 OTC의 잔류량은 조리 온도에 따라 감소될 것으로 추측 된다. Industrial advancements have resulted in food culture development, followed by increased seafood consumption and large-scale seafood farming, which has been accompanied by an increased prevalence of fish disease. The antibiotic oxytetracycline (OTC) is commonly used to prevent and treat bacterial diseases in fish. However, overuse of OTC had led to negative aspects. In view of this, we conducted a research with regard to aspects of remnants on olive flounder skin, liver, and muscle through dipping treatment and oral feeding of OTC and analyzed the results with bioassay and HPLC quantitative analyses. The dipping treatment was carried out once with 25 g/ton/hr of OTC, and the oral treatment with 62.5 ㎎/㎏ body weight/7 days. The results underwent a bioassay analysis. The dipping group reacted only on the skin right after dipping, while the oral feeding group responded on the skin for 77 days after feeding and on the muscle for 14 days. In the dipping group, the HPLC quantitative analysis revealed remnants in the skin on the 37th day and on the 13th day in the liver group. No remnants were found in the muscle, even immediately after dipping. In the oral feeding group, there was a high concentration (1.07 ㎎/㎏) of remnant in the skin, even on the 77th day. 0.56 ㎎/㎏ in the liver, even a small amount, and no remnant in the muscle on the 42nd day. To sum up, the results suggest that it will not be harmful to our body to observe the OTC withdrawal period of 40 days with the muscle because OTC will hardly remain on it. When using olive flounder for sashimi, the skin and liver should not be used for broth, as the quantity of OTC residue is several times higher than that found in muscle. As previous studies reported that the concentration of remnants gradually decreased with heating, so it was likely to lessen, depending on the cooking temperature.

토끼에서 oxytetracycline의 정맥 및 근육 투여시의 약물동태학

김은정,윤효인,박승춘,오태광,조준형,Kim, Eun-jung,Yun, Hyo-in,Park, Seung-chun,Oh, Tae-kwang,Cho, Chun-hyung 대한수의학회 1994 大韓獸醫學會誌 Vol.34 No.2

The study was carried out to determine the pharmacokinetic parameters after intravenous(iv) and intramuscular(im) administration (10mg/kr) in healthy rabbits. The results obtained through the experiments were summarized as follows: 1. Bioassay (Bacillus cereus 11778) was evaluated very useful for the determination of oxytetracycline(OTC) in the rabbit serum and tissues, with the detection limit of $0.125{\mu}g/ml$. 2. The pharmacokinetic profiles of OTC (10mg/kg, iv) in rabbits were best described with a two compartment open model $(C=29.5e^{-4,3t}{\pm}3.6^{-0.2t})$, whereas that of OTC (10mg/kg, im) showed a one compartment curve fitting. 3. Following iv administration, a rapid distribution phase was predominant [$t_{\frac{1}{2}}({\alpha}):1.43{\pm}0.98hr$ (♂), $0.5{\pm}0.1hr$(♀)], and then more slow elimination phase ensued [$t_{\frac{1}{2}}({\beta}):4.52{\pm}0.76hr$(♂), $7.32{\pm}2.52hr$(♀)]. Other computer generated pharmacokinetic values were as follows:C1 [$67.76{\pm}18.59ml/kg/h$(♂), $76.03{\pm}22.98ml/kg/h$ (♀)] Vd [$257.74{\pm}180.47ml/kg$ (♂), $92.33{\pm}23.62$ (♀)] AUC [$25.6{\pm}4.44mgh/L$ (♂), $39.6{\pm}12.13mgh/l$ (♀)]. There were no statistical significance between both sexes for all the parameters at the confidence level of 95%. 4. After im administaration, the absorption from the injection sites was very rapid [ Ka:$0.18{\pm}0.03h^{-1}$ (♂), $0.24{\pm}0.02h^{-1}$ (♀)] followed by a monoexponential elimination fashion. The time to peak blood level (Tmax) were calculated $1.64{\pm}0.15hr$ and $1.34{\pm}0.24hr$, in the male and female, respectively. The peak levels (Cmax) at the corresponding time were $1.69{\pm}0.23{\mu}g/ml$ (♂) and $2.08{\pm}0.16{\mu}g/ml$ (♀), with no statistical differences (p>0.05).

전복에 Oxytetracycline의 처리에 따른 잔류성 분석

김나영(Na-Young KIM),조희성(Hee-Sung JO),한지도(Ji-Do HAN),박민우(Min-Woo PARK),김진우(Jin-Woo KIM),김현정(Hyun-Jeong KIM),지보영(Bo-Young JEE),원경미(Kyoung-Mi WON) 한국수산해양교육학회 2015 水産海洋敎育硏究 Vol.27 No.1

Oxytetracycline (OTC) has been widely used in aquaculture field as a therapeutic and prophylactic agent because of its broad-spectrum activity against gram-positive and negative bacteria. Residual oxytetracycline (OTC) was studied after spray treatment of cultured abalone, Haliotis discus hannai. Muscle concentration of OTC was determined after spray treatment ( 4,000, 7,000, 10,000 ppm) in the abalone. Muscle samples were taken at 0, 1, 3, 7, 14, 21 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 day post-dose. OTC analyses were carried out by high performance liquid chromatography (HPLC). In 4000, 7000 and 1000 ppm treatment for small size abalones, OTC levels at 1 day post-dose, have been dramatically decreased by 8.34, 3.35 and 4.47 ug/g, respectively. For medium size abalones, concentration were measured as 7.58, 15.62 and 7.8 ug/g, respectively. Those of large size abalones also were observed as 11.31, 12.38 and 15.28 ug/g, respectively, at 1 day post-dose. No significant differences in residual OTC depletion in muscles were observed between the size of abalones. More than 0.2 mg/kg of OTC was detected in muscle tissues and the residues were found over 60 days after treatment. It is expected that these results would contribute to improve recommended withdrawl periods of OTC for a safer seafood supply.

Oxytetracycline/Tiamulin 복합제제의 병원성 미생물에 대한 항균작용과 돼지에서의 약물동태학적 연구

박승춘,윤효인,허원,최양웅,이원준,오태광 충남대학교 대학원 1994 論文集 Vol.14 No.-

The study was carried out to characterize the pharmacokinetic values after intravenous (iv, 20 mg/kg) and oral (po, 100 mg/kg) administration as mixture Oxytetracycline (OTC)/Tiamulin (TIA)in healthy pigs and to determine interaction between OTC and TIA against pig pathogenic bacteria. The results obtained through the experiment were summarized as follows: 1. The antibacterial effects of a combination of TIA and oxytetracycline OTC in vitro against Klebsiella pneumonia, Bordetella bronchoseptica, pasteurella multocida A, pasteurella multocida D,Actinobacillus pneumonia 2 type, Actinobacillus pnenmonia 5 type, Salmonella typhimurium,staphylococcus aureus were examined. There was a marked synergism between the two antibiotics against the test pathogenic organisms. 2. The pharmacokinetic profiles of OTC and TIA were best described with a two compartment open model (OTCl :C=11.93^e-0.76 t+4.446 ^e-0.09 t, TIA: C=27.97e^-2.06t +8.10e ^0.2t). 3. Following (20mg/kg, OTC/TIA) administration, a rapid distribution (OTC: t_(1/2)a 0.91±0.071, TIA:0.45±0.23) was predominant, and then more slow elimination phase ensued (t_(1/2)B, OTC:6.90±1.22시간 , TIA: 3.74±1.21). Other pharmacokinetic parameters calculated by computer programe were as follows ; [CI:170 ml/kg/h(OTC), 180 ml/kg/h(TIA)], [AUC:59.5 mg.h/L(OTC), 53.02 mg.h/L(TIA)]. 4. After po 100 mg/kg administration, the pharmacokinetic model was confirmed to two compartment open model the absorption was very rapid[K_10(h):0.33± 0.01(OTC), 0.26±0.056(TIA)] followed by a biexponential fashion. The time of peak blood level was calculated [Tmax 1.54±0.02 h (OTC), 4.22±0.14 h (TIA)].The peak levels (Cmax) at corresponding time were 4.10±0.01 ug/ml (OTC), 27.12±0.13 ug/m (TIA), respectively.

Oxytetracycline과 neomycin 복합제의 약욕에 따른 양식 넙치(Paralichthys olivaceus)의 근육내 잔류량 변화

김승민 ( Seung Min Kim ),전려진 ( Lyu Jin Jun ),정준범 ( Joon Bum Jeong ) 한국어병학회 2014 한국어병학회지 Vol.28 No.1

In the present study, we performed a dipping of olive flounder (average length and weight: 20±2.0 cm, 70±5.0 g) for a period of three hours a day, over two days, in a melted complex of oxytetracycline (OTC) and neomycin (N), by dissolving 25-10 ppm or 50-20 ppm in water. Subsequently, the remaining antibiotic density in muscle tissue collected from olive flounder was investigated, 1, 5, 14 and 40 days after discontinuation of the medication. 5 fish were used from each group. The standard graph drawn from the results of diluting two standard solutions of OTC and N based on various density levels, showed a relatively straight line with an R2 of 0.9999 and 0.9952, respectively. The recovery rate of OTC was shown to be 90-93% and N, 88-95%. Upon measurement of the remaining antibiotic density in the test group that had been exposed to 25-10 ppm of the complex of OTC and N, 0.97±0.084 μg/ml of OTC and 0.118±0.079 μg/ml N were detected on 1 day of the test. No antibiotic density was detected after day 5 of the test. Regarding the test group that were exposed to 50-20 ppm of the complex of OTC and N, 1.324±0.062 μg/ml of OTC and 0.788±0.05 μg/ml N were detected on day 1 of the test, and no antibiotic density was detected after day 5 of the test.