In vitro antibacterial activity, postantibiotic effects of norfloxacin and its interaction effects in combination with other antibiotics

박승춘,윤효인,오태광,Park, Seung-chun,Yun, Hyo-in,Oh, Tae-kwang The Korean Society of Veterinary Science 1997 大韓獸醫學會誌 Vol.37 No.1

국내에서 많이 사용되고 있는 제2세대 quinolone 항생제인 norfloxacin(NFX)에 대한 약역학적인 특성을 구명하기 위하여 국내에서 분리된 동물유래 병원성 세균에 대하여 시험관내에서 실험을 수행하여 다음과 같은 결과를 얻었다. 즉, E coli(n=89) 대한 NFX의 $MIC_{50}$와 $MIC_{90}$는 공히 0.02g/ml이었으며, Streptococcus spp.(n=36)에 대한 NFX의 $MIC_{50}$는 2g/ml 그리고 $MIC_{90}$는 4g/ml로 나타났다. Salmonella spp.(n=56)에 대한 NFX의 $MIC_{50}$와 $MIC_{90}$ 모두 0.2g/ml로 강한 항균력을 보였으며, Streptococcus spp.(n=24)에 대한 NFX의 $MIC_{50}$는 2g/ml 그리고 $MIC_{90}$가 4g/ml로 나타났다. Bacillus spp.(n=34)는 NFX의 $MIC_{50}$와 $MIC_{90}$는 모두 0.4g/ml으로서 대부분의 병원성 세균에 대해서 $MIC_{50}$와 $MIC_{90}$치가 동일하든지 또는 매우 비슷한 수치를 보여주었다. 그러나 NFX는 혐기성세균인 Clostridium spp.(n=34)에 대해서는 항균력이 매우 낮았다. 현재 수의임상에서 항균제 병용요법이 많이 응용되고 있는 것을 고려하여 NFX와 다른 항생물질간의 분획억제농도 (FICs)를 E coli 88ac을 시험균주로 하여 실험한 결과, NFX와 colistin과 병용할 때 FIC 값이 0.38로서 상승작용을 그리고 gentamicin, trimethoprim, amikacin, penicillin 및 tylosin과의 병용시 FIC 값이 각각 0.52, 0.56, 0.63, 1.00 및 1.02로서 상가작용을 보여주었으며, tetracyclin과의 병용시의 FIC값은 1.49로서 길항작용을 나타냄을 알 수 있었다. 한편 실제 항균제의 임상적용시 매우 주요한 요소인 항균활성후 저농도유효성(PAE)을 알아보기 위하여 E coli AB1157을 시험균주로 측정한 결과 PAE은 0.90~1.02 시간 그리고 S aureus R-209에 대해서는 PAE가 1.58~1.99 시간으로서 그람음성균 및 그람양성균 모두에 대해서 긴 PAE를 갖고 있음을 알 수 있었다.

국내토양에서 분리한 혐기성 세균 Streptococcus sp. An-21-1 이 생성하는 항생물질 II. 항생물질을 생성하는 혐기성 세균의 발효 및 항생물질의 분리 정제

박승춘,윤효인,오태광,Park, Seung-chun,Yun, Hyo-in,Oh, Tae-kwang 대한수의학회 1993 大韓獸醫學會誌 Vol.33 No.1

In order to search for new antibiotics from anaerobic bacteria, a large number of samples from domestic soil were collected and processed by apropriate methods. A potential strain, Streptococcus sp. An-21-1, was found to produce antimicrobial compounds. The Results were as follows; 1. During fermentation, the bacteria grew rapidly up to 20hr, thereafter entered the death phase. The optimal temperature and pH for the bacterial growth were $37^{\circ}C$ and pH 7.0, respectively. 2. Antibiotics were purified from culture broth by solvent extraction, silica gel column chromatography and Sepadex L.H 20 column. 3. Physicochemical properties of Ap-1 and Ap-2 were similar ; Their melting points were between $234-237^{\circ}C$. Color reactions of ninhydrin, 2,7-dichlorofluorescein, 4-dimethylaminobenzaldehyde, Dragendroffs reagent and 20% $H_2SO_4$, were positive. Therefore, we assumed that these antibiotics have amine group, immine group, alkaloid, and lipid components. These were stable to heat. UV spectrophotometry showed two peaks at 210 nm and 260 nm. From above results, we assumed these antibiotics are belong to the peptide antibiotic family.

국내토양에서 분리한 혐기성 세균 Streptococcus sp. An-21-1 이 생성하는 항생물질 I. 혐기성 세균의 선별과 동정

박승춘,윤효인,오태광,Park, Seung-chun,Yun, Hyo-in,Oh, Tae-kwang 대한수의학회 1993 大韓獸醫學會誌 Vol.33 No.1

Anaerobic bacteria are suggested to be potential source for new antibiotics. In order to search for antibiotics from domestic origin, we collected 800 soil samples across Korean locations and could isolate as many as 989 anaerobic strains. Among them 10, strains were found to have good producing capacity of antibiotics. An anaerobe was finally selected due to secreting antibiotics having high antimicrobial activity towards multiple resistant microorganism(E coli JM 83) transformed by genetic engineering technique. Its morphological, physiological and biochemical charateristics were investigated, together with antimicrobial spectrum therefrom. On antimicrobial spectrum study, substance secreted from this strain, had no activities to fungus and yeast. The selected strain showed G(+) and coccal shape, on Gram, staining and electron scanning microscopy, respectively. Biochemically this strain utilized glucose, fructose lactose, sucrose, but did not arabinose, cellulose, rhamnose, sorbitol, trehalose, mannitol. Catalase test showed negative property. Optimal growth temperature was $37^{\circ}C$. The results obtained above suggest this strain Streptococcus faecium subspp. and we named it Streptococcus sp. An-21-1.

Pharmacokinetic profiles of norfloxacin after intravenous and oral administration in the rabbits

박승춘,윤효인,오태광,조준형,Park, Seung-chun,Yun, Hyo-in,Oh, Tae-kwang,Cho, Joon-hyoung The Korean Society of Veterinary Science 1995 大韓獸醫學會誌 Vol.35 No.4

임상적으로 건강한 New Zealand White 종인 수컷 토끼에서 항생제 norfloxacin(NFX)의 체내 동태를 조사하기 위하여 체중 kg당 5mg을 정맥 및 경구 투여하였다. 그 결과 빠른 분포기와 소실기를 갖는 2-콤파트먼트 모델 양상으로 나타났다. 혈장에서의 약물분석은 HPLC로 실시하였는데, 이동상은 acetonitrile/0.01M phosphate buffer/ 10% citric acid 1mM heptane sulfonic acid(10/70/20)이었고, 흡수 파장은 274nm에서 실시하였다. 정맥 투여후, 생물학적 반감기는 3.14시간으로 나타났으며, 분포반감기는 0.38시간으로 빠른 분포를 보여주었다. 최고 혈중농도는 $24.27{\mu}g/ml$로 계산되었으며 청소율은 0.68ml/kg/h로 분석되었다. 경구 투여후, 최고 혈중 농도와 최고 혈중 도달 시간은 $0.86{\mu}g/ml$과 0.43시간으로 각각 계산되었다. 이때의 생물학적 반감기는 3.61시간으로 정맥 투여시와 유의성 있는 차이는 없었으며, 흡수 반감기는 0.17시간으로 빠른 흡수를 보여주었다. 생체이용율은 30%로 나타났으며, 0.2-1.6g/ml인 치료혈중 농도 범위에서 혈장 결합율은 26%로 나타나, 토끼에서 항생요법은 구강 투여시 초기 투여량은 2.71mg/kg이며, 유지 투여량은 12시간마다 2.54mg/kg이 적당한 것으로 분석되었다.

돼지호흡기세균에 대한 oxytetracycline과 tiamulin의 시험관내 상승작용 및 돼지에서의 약물동태학

박승춘,윤효인,이근우,Park, Seung-chun,Yun, Hyo-in,Lee, Keun-woo 대한수의학회 2002 大韓獸醫學會誌 Vol.42 No.1

The study was carried out to characterize the pharmacokinetics after intravenous (iv, 20 mg/kg) and oral (p.o. 100 mg/kg) administration as oxytetracycline (OTC) and tiamulin (TIA) mixture in swine and to determine interaction between OTC and TIA against various pig pathogenic bacteria. The antibacterial effects of OTC in combination with TIA in vitro showed synergistic effect against Salmonella typhimurium 1925, Pasteurella multocida Type A, P. multocida Type D, Krebsiella Pneumoniae 2001, K. Pneumoniae 1560, K. Pneumoniae 2208, Haemophillus pleuropneumonia S 2, and H. pleuropneumonia S 5, but against additive effect E. coli K88ab and S. choleraesuis on the basis of fractional inhibitory concentration (FIC) index. On the while, after i.v. and p.o. administration of OTC and TIA mixture, each OTC and TIA concentrations in plasma were fitted to an open two-compartment model. After i.v. administration of OTC-TIA mixture, the mean distribution half-life ($T_{1/2{\alpha}}$) of OTC and TIA in plasma showed 0.29 h and 0.17 h, and the mean elimination half-life ($T_{1/2{\beta}}$) of those was 4.36 h and 6.64 h, respectively. The mean volume of distribution at steady state ($Vd_{ss}$) of OTC and TIA was $0.85{\ell}/kg$ and $2.44{\ell}/kg$, respectively. After oral administration of OTC and TIA mixture, the mean maximal absorption concentrations ($C_{max}$) of OTC and TIA were $0.60{\mu}g/m{\ell}$ at 1.07 h ($T_{max}$) and $1.68{\mu}g/m{\ell}$ at 1.85 h ($T_{max}$), respectively. The mean elimination half-life ($T_{1/2{\beta}}$) of those showed 6.84 h and 6.36 h. In conclusion, we could suggest in this study that the combination of OTC and TIA may be recommended for the antibacterial therapy against polymicrobial infections, and both OTC and TIA showed large distribution to tissues and high $C_{max}$ after p.o. administration.

돼지에서 근육주사한 Abamectin에 대한 HPTLC 분석 및 약물동태학

박승춘,윤효인,Park, Seung-chun,Yun, Hyo-in 대한수의학회 2000 大韓獸醫學會誌 Vol.40 No.1

We established a new method to analyze abamectin using HPTLC (high performance thin layer chromatography) in order to obtain its pharmacokinetic profiles in pigs. Recovery of abamectin in pig serum after fluorescence derivatization was $80.01{\pm}3.82%$ at 0.1ppm and $83.67{\pm}3.63%$ at 10ppm, respectively. Detection reproducibility in terms of coefficient variation (c.v.) was 3.09% and 2.74% (intra-day), and 3.71% and 51.7%(inter-day), for 0.1 and 10ppm, respectively. Pharmacokinetics of abamectin was studied in five Yorkshire-Landrace mixed bred male pigs ($35.0{\pm}2.7kg$) administered intramuscularly 0.3mg/kg b.w. Pharmacokinetic profiles of abamectin in pigs were described by the 1-compartment open model with first-order absorption and first-order elimination. AUC (area under the curve) was $262.65{\pm}16.44ng{\cdot}day/ml$ and the biological elimination half-life ($t_{1/2},\;k_e$) was $5.28{\pm}0.84$ days, indicating somewhat high bioavailability and long half-life by the intramuscular route. We suggest intramucular injection of abamectin could be also used in place of the recommended route of its subcutaneous administration so far.

축산현장에서 Quinolone 제제 사용현황 및 규제동향

박승춘(Seung-Chun Park) 한국보건교육건강증진학회 2005 한국보건교육·건강증진학회 학술대회 발표논문집 Vol.- No.-

Recombinant Bovine Somatotropin의 피하주사 후 Male과 Female Rat에서 약물동태 및 조직분포

박병권,박승춘,윤효인,Park, Byung-kwon,Park, Seung-chun,Yun, Hyo-in 대한수의학회 2003 大韓獸醫學會誌 Vol.43 No.2

The purpose of this study is to investigate the pharmacokinetics and tissue distribution of recombinant bovine somatotropin (rBST) after subcutaneous adminstration of $^{125}I-rBST$ in male and female rats. A solid state conjugation (Iodo-bead$^{(R)}$) method was confirmed useful for producing $^{125}I-rBST$ because the administration of the conjugated form enabled enough to determine time- concentration relationships of rBST in rats. Subcuatenous administrations showed sex differences that female ($t_{1/2,kc}$, 2.87 h) revealed rapid elimination as compared to male ($t_{1/2,ke}$, 4.81 h), with the absorption ($t_{1/2,ka}$ in male being 0.3 h and that in female 0.75 h) in the reverse order. For subcutaneous administration of rBST in male rats, the liver was the highest in amount, followed by kidney, testes, muscle, and stomach, at the slaughtering tame of 1, 6, 12 and 24 h. But the testes was the highest at the 48 h slaughtered animals, followed by liver, kidney, stomach, and muscle. In slaughtered females at 1, 6, and 12 h after the administration of rBST, the liver was the highest, followed by ovary, kidney, small intestine, and stomach. At 24 and 48 h slaughtered female rats, the ovary was the highest, the liver the second, and the kidney the third.

가죽나무 추출물의 꽃매미 유인효과, 항산화 활성 및 국소자극성시험

이승진,박승춘,Lee, Seung-Jin,Park, Seung-Chun 대한수의학회 2013 大韓獸醫學會誌 Vol.53 No.4

This study aimed to assess the attraction effect against Lycorma delicatula and antioxidant activity of hexane, chloroform, butanol and water fraction obtained from Ailanthus altissima methanol extract. The attraction effect of chloroform fraction showed the highest activity (47%) as compared to that of other fractions. In the DPPH radical scavenging activity, methanol and butanol fraction showed higher antioxidant activity than other solvent fractions. From the above results, the potential chloroform fraction was further performed by local irritation test in New Zealand white rabbits. In eye irritation test, chloroform fraction showed moderate irritant at high concentration 0.5 g/site/mL, but there was no eye irritation at low concentration (0.05 g/site/mL). In accordance with the Draize evaluation of skin irritation, the primary irritation index was calculated to 3.3 and 0.68 at high (0.5 g/site/mL) and low concentration (0.05 g/site/mL) causing moderate and mild irritation, respectively. On the basis of this study, Ailanthus altissima chloroform fraction could be safely considered to be a candidate of attractant against Lycorma delicatula.

돼지와 랫트에서 sulfamethazine의 약물동태학 및 조직분포

윤효인,박승춘,오태광,조준형,박종명,Yun, Hyo-in,Park, Seung-chun,Oh, Tae-kwang,Cho, Joon-hyoung,Park, Jong-myeong 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.2

In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.