Carbenicillinに関する基礎的研究

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タイトル別名
  • FUNDAMENTAL STUDIES ON CARBENICILLIN
  • Carbenicillin ニ カンスル キソテキ ケンキュウ

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説明

In vitro and in vivo evaluations as well as absorption excretion, and distribution in the body were investigated with carbenicillin, a new semi-synthetic penicillin. This antibiotic has a wide spectrum against Gram-p ositive and Gram-negative species of bacteria, especially active at a certain level against strains of Pseudomonas aeruginosa and Proteus group, which are highly resistant to ampicillin. It seemed likely that this drug possessed a certain stability against penicillinase because of the fact that some of the ampicillin-resistant strains showed to be considerably sensitive to carbenicillin.<BR>In vitro activities of c arbenicillin were not so markedly influenced by the kinds and pH of test medium, and the addition of serum to the medium, but changes of the inocula sizes caused considerable changes in MIC values. The MIC level of carbenicillin acted bactericidally. Repeated subculture of staphylococci and E. coli in nutrient broth containing increasing levels of carbenicillin resulted a step wise development of resistance, the rate of which was more rapid in E. coli than in staphylococci.<BR>Subcutaneous treatments of experimental mice infections by various bacteria with carbenicillin were proved to be effective, if the causative organisms were sensitive in vitro against this drug.<BR>Carbenicillin was administered by intramuscular injection to rabbit, rat and dog as a single dose of 20 m g/kg, and the levels of the drug in serum, urine, bile and tissues were investigated. Both in do g and rabbit peak serum levels were obtained 30 minutes after administration about 12. 5∼30 mcg/ml in rabbit and 15 mcg/ml in dog. The amounts of carbenicillin excreted in the urine during the first 7 hours in rabbit fluctuated between 65% and 80% of the given dose, and those excreted in the bile during the first 4 hours in rat fluctuated from 12 to 18% of the given dose. Tissue concentrations were relatively high in liver and kidney.<BR>In human volunteers, thin layer chromatography and agar-gel electrophoresis of the urine sample showed that the antibiotic was excreted into the urine without conversion to penicillin G after intramuscular administration.

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