• Title/Summary/Keyword: DW116

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Antigenicity of DW-116, a New Quinolone Antibiotic, in Guinea Pigs rind Mice (기니픽과 마우스에서 신규 퀴놀론 항균제 DW-116의 항원성 시험)

  • 권현진;한형미;이흠숙;정용호;윤성호;이문선;이덕근
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.165-170
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    • 1998
  • Antigenic potential of DW-116, a newly synthesized fluoroquinolone, was examined by conduc-ting active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. In ASA test, mild to moderate signs of anaphylactic responses were observed in the groups sensitized with low (2 mg/body) and high (10 mg/body) doses of DW-116 alone and the group sensitized with DW-116 plus adjuvant. Some moderate to severe anaphylactic reactions were observed in the group sensitized with a DW-116-bovine serum albumin (BSA) conjugate plus adjuvant when challenged with a DW-116-guinea pig senHn albumin (GSA) conjugate. However these reactions were considered to be a cross-reaction between BSA and GSA since similar reactions were induced when challenged by GSA alone. In heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In PHA test, positive responses were observed in the groups sensitized with low and high doses of DW-116 alone and the group sensitized with DW-116 plus adjuvant. However, these responses were not considered to be drug-specific because some positive responses were also seen in the negative control group. From these results, it was concluded that DW-116 is not likely to have specific antigenic potential in clinical use.

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Bactericidal Activities of DW-116, a New Quinolone (새로운 퀴놀론 항균제 DW-116의 살균 작용)

  • 최금화;오태권;권애란;김병각;최응칠
    • YAKHAK HOEJI
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    • v.43 no.1
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    • pp.131-133
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    • 1999
  • The bactericidal activities of DW-116, a new fluoroquinolone was estimated by comparing the minimal bactericidal concentrations (MBCs) of it against some Gram-positive and -negative bacterial strains with the minimal inhibitory concentrations (MICs). The MBCs against the test organisms were equal to or two times higher than MICs. The results support that the antibacterial activity of DW-116 is bactericidal.

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Jn vivo and Jn vivo Antibacterial Activity of DW-ll6, a New Quinolone Antibiotic (신규 퀴놀론 항균제 DW-116의 in vivo 및 in vivo 항균활성)

  • Hwang, Yun-Ha;Han, Kyung-Oh;Lee, Jin;Yang, Hee-Bog;Chung, Yong-Ho;Yoon, Sung-June;Lee, Dug-Keun
    • Biomolecules & Therapeutics
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    • v.5 no.2
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    • pp.187-193
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    • 1997
  • The in vivo and in vivo antibacterial activity of DW-116, a newly synthesized fluoroquinolone, were compared with those of other quinolones. DW-116 exhibited more potent antibacterial activity than rufloxacin and lower activity than ofloxacin and ciprofloxacin in in vivo assay But, DW-116 particularly showed strong activity against the family of staphylococci including methicillin-sensitive staphylococcus and its activity was more active than that of ciprofloxacin. The time-kill curve studies showed rapid bactericidal activity for DW-116. The post-antibiotic effect of DW-116 was observed between 0.66 and 5 hours. The therapeutic efficacy of DW-116 against respiratory infection with P. aeruginosa was as strong as that of ciprofloxacin and its effect against urinary tract in(traction with E. coli was more effective than rufloxacin. The excellent therapeutic efficacy of DW-116 against these local infections is due to its good pharmacokinetic profiles.

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Micronucleus Test of DW-116, a Novel Antibacterial Quinolone (신규 퀴놀론 항균제 DW-116의 소핵시험)

  • Moon, Eun-Yi;Lee, Jin;Choi, Chung-Ha;Lee, Chi-Woo;Chung, Yong-Ho;Yoon, Sung-June;Lee, Dog-Keun
    • Biomolecules & Therapeutics
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    • v.4 no.3
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    • pp.239-243
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    • 1996
  • DW-116 {(1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride) is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the appearance of micronucleus in polychromatic erythrocytes (PCEs) of mouse bone marrow cells after intraperitoneal and oral single administration. We prepared the bone marrow cells at 30hr after drug administration and they were used for measuring PCE with micronucleus. The results showed there was no statistically significant increase in the numbers of PCEs with micronucleus in all DW-116 administered groups compared with a negative control group. The results also showed that the ratio of normochromatic erythrocytes(NCEs) to PCEs of all DW-116 administered groups was not significantly different from that of a negative control group. These results suggested that DW-116 may not cause any chromosomal damage and it has no in vivo mutagenic potential under these experimental conditions.

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Post-Antibiotic Effect of DW-116, a New Quinoloen (새로운 퀴놀론 항균제 DW-116의 Post-Antibiotic Effect)

  • Choi, Keum-Hwa;Oh, Tae-Kwon;Baek, Moon-Chang;Kim, Byong-Kak;Choi, Eung-Chil
    • YAKHAK HOEJI
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    • v.42 no.2
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    • pp.229-231
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    • 1998
  • The post-antibiotic effects (PAE) of DW-116 were evaluated against Bacillus subtilis ATCC 6633, Bacillus cereus ATCC 27348, Staphylococcus aureus ATCC 25923 , Escherichia coli ATCC 25922 and Pseudomonas aeruginosa MB4-16, repectively. Against gram-positive bacteria, PAEs of DW-116 were longer duration (20-35 min) than those of rufloxacin(1O-20 min), and shorter than those of ciprofloxacin (50-90 min). Especially, against E. coli, DW-116 and ciprofloxacin obtained approximately 3 hrs of PAES.

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Resistance Mechanism of Acinetobacter spp. Strains Resistant to DW-116, a New Quinolone

  • Choi, Keum-Hwa;Baek, Moon-Chang;Kim, Byong-Kak;Choi, Eung-Chil
    • Archives of Pharmacal Research
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    • v.21 no.3
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    • pp.310-314
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    • 1998
  • DW-116 is a new fluoroquinolone antimicrobial agent with a broad spectrum. In order to elucidate the resistance mechanism to DW-116 in Acinetobacter spp. bacteria, total chromosomal DNA was isolated from 10 strains of Acinetobacter spp. resistant to DW-116. Quinolone resistance determinant region (QRDR) of DNA gyrase gene was amplified by PCR. The 345 bp nucleotide fragment yielded was inserted into pKF 3 which was used as the vector. Comparisons of the DNA sequences of 8 strains with that of the wild type strain revealed a Ser-83 to Leu mutation in mutants and all ten strains contained one silent mutation$(T{\rightarrow}G)$in QRDR. From Acinetobacter MB4-8 strain, DNA gyrase was isolated and purified, through novobiocin-sepharose, heparin-sepharose affinity column chromatography. The enzyme was composed of two subunits and the molecular mass of subunits A and B were 75.6 and 51.9 kDa, respectively. The supercoiling activity of the reconstituted DNA gyrase composed of subunit A from Acinetobacter MB4-8 and subunit B from E. coli was not inhibited by $128{\mu}\textrm{g}$ml of ciprofloxacin. It might be said that one of the resistance mechanisms to DW-116 in Acinetohacter MB4-8 was subunit A alteration of DNA gyrase.

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Immunomodulating Activity of DW-116, A New Quinolone Antibiotic

  • Moon, Eun-Yi;Choi, Chung-Ha;Pyo, Suh-Kneung;Chung, Yong-Ho;Yoon, Sung-June;Lee, Dug-Keun
    • Archives of Pharmacal Research
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    • v.21 no.5
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    • pp.610-614
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    • 1998
  • DW-116, [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquino-line-3-carboxylic acid hydrochloride}, is a new quinolone antibiotic with a broad antibacterial spectrum against G(+) and G(-) bacteria. DW-116 was evaluated for the immunomodulating activities, which is one of the efforts to investigate the mechanism of action related to the good in vivo antibacterial efficacy. The results of in vitro studies revealed there was no statistically significant increase in B and T lymphocyte proliferation. But the results of in vivo studies showed that the number of plaque forming cells (PFC), the amount of polyclonal antibodies and delayed-type hypersensitivity (DTH) were significantly increased after the repeat administration with 12 and 60 mg/kg of DW-116. Taken together, these results proposed that immunostimulting effect of DW-116 could be one of the action mechanisms for demonstrating in vivo antibacterial activities under these experimental conditions.

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Placental Transfer and Pharmacokinetics of a Single Oral Dose of the Fluoroquinolone Antibacterial DW-116 in Rats (랫드에서 fluoroquinolone 항균제 DW-116의 단회 경구투여에 의한 태반통과와 약물동태연구)

  • 김종춘;신호철;허정두;이종화;정문구;윤효인
    • Biomolecules & Therapeutics
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    • v.10 no.1
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    • pp.43-49
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    • 2002
  • The present study was conducted to investigate the placental transfer and pharmacokinetics of the flu-oroquinolone antibacterial DW-116 in pregnant rats. The placental transfer and pharmacokinetics of DW-116 were examined after a single oral dose of 500 mg $^{14}C$ DW-116/kg on gestational day 18. Maternal and fetal tissues were collected at 0.17 0.5,1,2,4,8, and 24 h after dosing. Maximum radioactivity was detected in maternal plasma, placenta, and whole fetus at 1 h, and in amniotic plasma at 4 h after dosing. Thereafter, radioactivity gradually disappeared from these tissues and was 16~28% of maximum levels at 24 h after dosing. Radioactivity in whole fetus were higher than those in the maternal plasma and placenta. The $T_{1/2,abs}$, $T_{1/2,{\beta}},$ AUC, $T_{max},$ and $C_{max}$ in the maternal plasma were approximately 6 min, 13.3 h, 1620 $ug^*hr/ml,$ 0.5 h, and 136 ug/ml, respectively. Those in the placenta were approximately 20 min, 12.3 h, 2150 $ug^*h/$m\ell$,$ 1.0 h, and 172 ug/ml, respectively. Those in the whole fetus were 13 min, 12.8 h,2549 $ug^*h/$m\ell$,$ 1 h, and 191 ug/ml, respectively. In the amniotic fluid of maternal uterus, the 4T_1/2,abs}$, $T1/2,{\beta},$ AUC, $T_{max},$ and $C_{max}$ were approximately 1.3 h,9.3 h,2508 $ug^*h/$m\ell$,$ 4.4 h, and 135 ug/ml, respectively. While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid. In conclusion, this study demonstrated that the absorption and distribution of DW-116 in maternal plasma and placenta were extensively rapid, and that the test chemical well passed the blood-placenta barrier and was transferred to the fetus.

Metabolism and Excretion Study of DW116, A New Fluoroquinolone, in Rats

  • Jung, Byung-Hwa;Park, Young-Han;Park, Jongsei;Chung, Bong-Chul
    • Archives of Pharmacal Research
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    • v.20 no.4
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    • pp.358-362
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    • 1997
  • Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1 -piperazinyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential. Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound, $^{19}$ F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were $28.6{\pm}2.7% $and $36.4{\pm}1.8%$ of the administered dose and the corresponding biliary recoveries were $14.4{\pm} 5.5%$ and $37.0{\pm}7.6%$, respectively.

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Development Toxicity Evaluation (랫드에서 표준 및 사료제한 시험에 의한 fluoroquinolone 항균제 DW-116의 발생독성평가)

  • 김종춘;윤효인;이희복;한상섭;정문구
    • Journal of Life Science
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    • v.11 no.5
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    • pp.447-456
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    • 2001
  • We have recently demonstrated that the fluoroquinolone antibacterial DW-116 caused a significant developmental toxicity in rats. The present study was conducted to determine whether the development toxicity induced by DW-116 treatment was the result of malnutrition fro reduced food intake or the direct effects of test chemical on conceptuses. The test chemical was administered by gavage to pregnant rats from gestational days 6 through 16 at dose levels of 0 and 500 mg/kg/day. A pair-feeding study was also performed in which the pregnant rats received the same amount of diet consumed by the DW-116-treated pregnant rats. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for examined for external, visceral, and skeletal abnormalities. In this treatment group, the maternal toxicities included increased abnormal clinical signs, decreased maternal body weight, suppressed body weight gain during treatment and posttreatment periods, and reduced food intake. The significant developmental toxicities included increased fetal deaths, decreased live fetuses, reduced fetal body weight and placental weight, increased incidence of fetal abnormalities, and increased fetal ossification delay. In this pair-fed group, however, slight maternal toxicities including decreased body weight and suppressed body weight gain during treatment period were observed in comparison with the control group, and minimal development toxicities including reduced fetal and placental weights and increased fetal ossification delay were found. The number of fetal deaths and live fetuses, and the incidences of malformed fetuses and litters with affected fetuses were comparable to the control values. Based on the results, it could be concluded that the development toxicity observed in the treatment group is attributable to the direct effects of Dw-116 treatment, but not to the maternal malnutrition from reduced food consumption during pregnancy.

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