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.

시험관내에서 Enrofloxacin과 Colistin의 병용투여시 상호작용과 항균물질들의 독소중화능

박승춘,김민규,윤효인,오태광 한국독성학회 1997 Toxicological Research Vol.13 No.1

In the present study, we investigated the neutralization activity of various antimicrobials against lipopolysaccharide (LPS) as well as interaction between two antimicrobials (enrofioxacin and coilstin) using checkerboard method. The neutralization activity of antimicrobials used in the test was assayed by means of LAL chromogenic test after reaction of LPS with colistin, enorfioxacin, ampicillin, polymyxin B, oxytetracycline, streptomycin, and erythromycin. As the results, the neutralization activity of coltstin and polymixin B had a more stronger than that of tested other antimicrobials. In bacterial culture broth, the best neutralization activity of the antibiotics was also shown to coltstin and polymixin B. Meanwhile, It was shown to have synergism between enorfloxacin and coltstin on the basts of FIC (fractional inhibition concentration). The FIC of enorfioxacin-colistin combinations was 0.50-1.03 to Staphylococcus aureus R-209, 1.03-1.06 to Salmonella typhimurium, 0.75-1.25 to Bordetella Bronchtseptica and 1.02-1.25 to E. coli K88ab. On the basts of the above results, the present study may be of clinical usefulness in the choice of an antibiotic therapy for severe sepsts in animals.

[시론] 호국보훈의 달, '상기하고 감사하자'

박승춘 평화문제연구소 2011 통일한국 Vol.330 No.-

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.

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.

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

박승춘,상지강,오병철,김종춘,정규식,이명헌,윤효인,Mi-Hyun Hwang 대한수의학회 2007 Journal of Veterinary Science Vol.8 No.4

The pharmacokinetics and dosage regimen of norfloxacin- glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t1/2α) and elimination half-life (t1/2β) were 0.36 ± 0.07 h and 7.42 ± 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vdss) was 4.66 ± 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (Cmax) was 0.43 ± 0.06 μg/ ml at 1.36 ± 0.39 h (Tmax). The mean absorption (t1/2ka) and elimination half-life (t1/2β) of NFLXGA were 0.78 ± 0.27 h and 7.13 ± 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 ± 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.

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.

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 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.

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.