In vivo Evaluation of a Novel ${\beta}-Lactam$ Antibiotics, YH-487

새로운 ${\beta}-Lactam$계 항생물질 YH-487의 in vivo 항균활성

  • Won, Yu-Jung (Laboratory of Biotechnology, Yuhan Research Center) ;
  • Kang, Heui-Il (Laboratory of Biotechnology, Yuhan Research Center) ;
  • Lee, Jong-Wook (Laboratory of Biotechnology, Yuhan Research Center) ;
  • Chung, Dong-Hyo (Department of Food Technology, Chungang University)
  • 원유정 ((주)유한양행 중앙연구소) ;
  • 강희일 ((주)유한양행 중앙연구소) ;
  • 이종욱 ((주)유한양행 중앙연구소) ;
  • 정동효 (중앙대학교 산업대학 식품공학과)
  • Published : 1997.04.28

Abstract

A novel compound, named YH-487, was synthesized by attaching the thiol and aminothiazole residue to $C_3$ and $C_7$ position of 7-aminocephalosporanic acid (7-ACA). The therapeutic efficacy on infected animals, pharmacokinetics in vivo and the effect on intestinal microflora of YH-487 were examined. The pharmacokinetics of YH-487 were similar to that of cefotaxime, a third generation ${\beta}-lactam$ antibiotics, in rat. Upon in vivo administration, YH-487 was predominantly delivered to kidney, and mostly excreted through kidney without making any metabolites. The therapeutic efficacy of YH-487 to animal infected with E. coli was three times and twenty times higher than that of cefotaxime and cefotiam, respectively, In vivo administration of YH-487 to Sprague-Dawley rats significantly decreased the population of intestinal gram negative species such as Enterobacteria and Barteroides. However, no significant changes were obseved in gram positive species such as Lactobacillus, Bifidobacteria and Staphylococcus. In addition, continuous administration of YH-487 did not increase the possibility to induce resistant strains in intestinal microflora.