• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.196-203
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• 1993

We compared in vitro antibacterial activity of DWC-751, a new parenteral cephalosporin antibiotic, with those of cefpirome (CPR), cefotaxime (CTX) and ceftazidime (CAZ). DWC-751 showed a broad antimicrobial spectrum against Gram-positive and negative bacteria. The antibacterial activity of DWC-751 against Stapylococcus aureus was equal to that of CPR and superior to those of CTX and CAZ. The activity of it against Excherichia coli was more potent than those of CPR, CTX and CAZ. Against Pseudomonas aeruginosa, DWC-751 was slightly inferior to that of CAZ and superior to those of CPR and CTX. The antibacterial activity of DWC-751 was superior to those of CPR, CTX and CAZ against clinical isolates and ofloxacin resistant strains. DWC-751 showed bactericidal action against Escherichia coli at concentrations close to the MIC and induced the formation of filament and burge and lysis of Escherichia coli in a microscopic examination.

• Toxicological Research
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• v.11 no.1
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• pp.109-116
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• 1995

Single intravenous and oral administration to SD rats and ICR mice of both sexes were performed to investigate the acute toxicity of DWC-751, a new parenteral cephalosporin. $LD_50$ values for ICR mice and SD rats administered intravenously with DWC-751 were as follows; 1151.1 mg/kg (male SD rat), 1183.5 mg/kg (female SD rat), 2698.1 mg/kg (male ICR mouse), 2833.0 mg/kg (female ICR mouse). It is suggested that $LD_50$ values in rats and mice of both sexes would be 5000 mg/kg in oral route. Major general symptoms induced by injection intravenously with DWC-751 are decreased motor activity, increased respiratory rate, tremor and convulsion. In oral route, piloerection and soft stool are observed to 4 day after administration. No significant body weight changes were observed at any level in the groups administered with DWC-751. The gross finding of rats administered intravenously was observed cecum distension.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.103-108
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• 1993

The synthesis and physicochemical properties of a novel cephalosporin, DWC-751 are described. DWC -751, (6R , 7R)-7-[ (Z)-2-(2-aminothiazol-4-yl)-2- methoxyiminoacetamido]-3-[(1-methylbenzotriazol-3-ium) methyl]-ceph-3-em-4-carboxylate monosulfate($IV_{\alpha}$) was conveniently obtained by the conversion of compound (IV) into the crystalline monosulfate. Adjusting pH 4.8-5.2 in aqeous solution of the crude crystalline, compound(IV) in the form of a crystalline pentahydrate was prepared with a high degree of purity. The influence of the various organic and inorganic acids on the solubility of compoud(IV) and its salts, was examined. Particularly, the solubility of DWC-751 was 92 mg/mι at pH 1.7 and 233 mg/mι at pH 3.0. DWC-751 showed a broad antimicrobial spectrum against gram-positive and negative bacteria.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.204-210
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• 1993

The distribution and excretion of DWC-751, a new cephalosporin, were examined in rats and mice following a single intravenous administration. DWC-751 in plasma and urine was determined by both HPLC and microbiological assay. The plasma concentration of the drug declined biexponentially. The initial and terminal half lives of the drug were 3.0 and 28.3 min, respectively. Binding of the drug to plasma proteins was 42.3%. The distribution volume at steacly-state ($Vd_{ss}$) was only 0.341 ι/kg, which is well correlated with the low n-octanol/water partition coefficient of the drug ($K_{o/w{\cong}0$) Actually, the drug was distributed to liver, kidney and lung with very low organ/plasma concentration ratio. The drug, was excreted mainly via renal excretion, i.e., the total($CL_T$) and apparent renal($CL_{R}$) clearances of the drug were 10.8 and 7.5 ml/min/kg, respectively.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.106-106
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• 1993

DWC-751은 그람양성 및 음성균주에 대하여 광범위한 항균스펙트럼을 가지는 것으로 나타났다. 그람양성균 S. aureus에 대하여는 cefpirome과 동등하며, cefotaxime 보다 4배, ceftazidime보다 16배 우수하였고 그람음성균에 대하여 DWC-751의 항균력은 cefpirome, cefotaxime보다 2배, ceftazidime보다 4-8배 우수하였다. Ps. aeruginosa에 대한 DWC-751의 항균력은 ceftazidime과 거의 동등한 항균력을 나타내었고, cefpirome보다 2배, cefotaxime보다 4-8배 우수한 항균력을 나타내었다. 임상분리균주 및 ofloxacin 내성균주에 대한 DWC-751의 항균력은 표준균주에 대한 결과와 같이 대조약물보다 우수하였다. 전신감염치료효과에 있어서 Streptococcus pyogenes, Serratia marcescens, Acinetobacter calcoaceticus, Morganella morganii, Proteus mirabilis에 대한 동물실험 결과, ED$_{50}$치에 의한 효능은 cefotaxime 보다 우수하였으며,Enterobacter cloacae, Pseudomonas aeruginosa에 대하여는 ceftazidime과 거의 동등하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.105-105
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• 1993

랫드 및 마우스에 1회 경구 및 정맥투여하였을때의 급성독성을 관찰한 결과 랫드에서 급성경구 시험결과의 LD$_{60}$치는 암수 각각 5,000mg/kg 이상이었으며, 급성정맥시험 결과의 LD$_{50}$치는 수컷에서 1,151mg/kg, 암컷에서 1,184mg/kg이었다. 마우스에서 급성경구시험 결과의 LD$_{60}$치는 암수 각각 5,000mg/kg 이상이었으며 급성정맥시험 결과의 LD$_{50}$치는 수컷에서 2,698mg/kg, 암컷에서 2,833mg/kg이었다. Sal. typhimurium을 이용한 돌연변이시험, 마우스를 이용한 소핵시험, 배양세포를 이용한 염색체 이상 시험을 실시한 결과 모두 음성으로 나왔으므로 DWC-751의 돌연변이 유발능은 없는 것으로 나타났다.타났다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.107-107
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• 1993

결과 및 고찰: 이 약의 흰쥐에서의 체내동태는 혈중농도로 볼 때 2-exponential pharmacokinetics에 따르고, HPLC법으로 정량한 경우의 $T_1$/$_2$$\alpha$, $T_1$/$_2$$\beta$, AUC, C $L_{T}$, C $L_{R}$, V $D_{SS}$ 는 각각 1.90min, 21.89min, 1899.36$\mu\textrm{g}$ㆍmin/ml, 10.66ml/min/kg, 7.48ml/min/kg, 0.28l/kg으로 bioassay법과는 약간의 차이를 보였다. 분포특성은 간장과 신장에 많이 이행하였으며, 폐로의 이행도 적지만 관찰되었다. 이 약의 단백결합률은 그 농도가 31.3$\mu$M일 때 42.3%였고 water/n-octanol계에서의 유상으로의 분배는 거의 일어나지 않았다. 이 약의 분포용적이 작은 것은 단백결합 때문이라기보다는 높은 극성때문으로 추정되었다. 이 약의 C $L_{R}$은 GFR의 문헌치보다 컸으며 C $L_{T}$의 약 2/3을 차지하므로 약물소실에 있어서 신장의 기여도가 크고 신배설 과정에 신분비가 관여하고 있음을 알 수 있었다. 이런 사실은 CAZ나 CTX등의 기존 세파계 항생제들과 유사했으며, 추후 다회투여시와 용량의존적 체내동태에 관해 더 많은 연구가 필요하리라 생각되었다.되었다.