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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록· 키워드
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${\beta}-Lactamase$ stability, chemotherapeutic activity, and pharmacokinetics of 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN1), 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN2), pivaloyloxymethyl-7-[(Z)-2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN1P), and pivaloyloxymethyl-7-{(Z)--2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN2P) were examined. CEN1, CEN2, CEN1P, and CEN2P were very stable to the ${\beta}-lactamase$ obtained from three strains(Enterobacter cloacae P99, Escherichia coli TEM, and Citrobacter freundii). Chemotherapeutic activities$(ED_{50})$ of CEN2 and CEN2P against experimental systemic infections due to Streptococcus pyogenes 77A and Escherichia coli 078 were superior to those of CEN1 and CEN1P, respectively. The $ED_{50}$ values of CEN1, CEN2 were 5.82 mg/kg, 0.89 mg/kg(s.c., S. pyogenes 77A) while those of CEN1P, CEN2P were 14.56mg/kg, 6.40mg/kg(p.o., S. pyogenes 77A), respectively. The pharmacokinetics of CEN1, CEN2, CEN1P, and CEN2P were investigated in mice and rats. In mice, peak blood levels of $1.25\;{\mu}g/ml$ were recorded within 20 min after oral administration of a single dose equivalent to 40 mg/kg CEN1P. Cmax of CEN1P was much higher than that of CEN1 in mice and rats. Oral absorption of CEN2P was much higher than that of CEN2.
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