- 著者
- 四辻 彰 伊東 優子 保田 隆 才川 勇 大角 誠治 矢野 三郎 上田 泰
- 出版者
- 公益社団法人 日本化学療法学会
- 雑誌
- CHEMOTHERAPY (ISSN:00093165)
- 巻号頁・発行日
- vol.36, no.4, pp.294-303, 1988
Compromised host の対象として高齢者を取り上げ, その血清中での β-lactam 系抗生剤の sub-minimum inhibitory concentration (sub-MIC) シこおける抗菌作用を調べた。各血清60μl に薬液10μl を加え, それに菌懸濁液10μl を接種し 37℃ 4時間培養後, 生菌数の増減を測定した。高齢者の血清殺菌力は健常者に比べ <I>Escherichia coli</I> および <I>Klebsiella pneumoniae</I> に対しては弱まっている例が多かった。<I>Proteus</I> <I>mirabilis</I> T-277 株に対しては約半数例で高齢者の血清殺菌力は強まっていたが, T-250株 に対しては強まっている例はなかった。また<I>Proteus vulgaris</I>。<I>Pseudomonasaeruginosa</I> および<I>Staphylococcus aureus</I> に対しては健常者と同等の殺菌力であった。この殺菌因子として非働化で弱められる易熱性物質やペントナイト処理で除かれるリゾチームの関与が推定された。次に高齢者血清中での beta-lactam 系抗生剤の sub-MIC での殺菌作用をみると, pipera-cillin, cefoperazone および cefbuperazone は nutrient bmth (NB) 中でも高齢者血清中でも殺菌的または静菌的に作用した。一方 carbenicillin, cefazolin および cefmetazole は NB 中では菌の増殖を阻止したが高齢者血清中ではほとんど抗菌作用を示さなかった。
- 著者
- 才川 勇 高井 明 中島 良文 吉田 長作 保田 隆 清水 悦郎 酒井 広志 滝 秀雄 田井 賢 高下 寛
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.97, no.10, pp.1071-1081, 1977-10-25 (Released:2008-05-30)
- 参考文献数
- 10
- 被引用文献数
- 5 3
Metabolism of 6-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido) phenylacetamido] penicillanic acid (T-1220), a new β-lactam antibiotic, was studied in vivo and in vitro. Only unchanged T-1220 was detected by bioautography in urine of human, monkeys, dogs, rats, and mice receiving T-1220 intramuscularly. When 14C-labeled T-1220 was administered to rats, most of the radioactive product was excreted unchanged in the urine, but two metabolites were detected in a minute amount by autoradiography. These metabolites were identified as 14C-labeled α-{3-[2-(N-ethyl-N-oxaloamino) ethyl] ureido}-benzylpenicillin (14C-T-1220A) and 14C-labeled α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido) benzylpenicilloic acid (14C-T-1220B) by thin-layer chromatography, electrophoresis, and high-pressure liquid chromatography. Metabolism of 14C-T-1220 and its mechanism were studied by using high-pressure liquid chromatography for the separation and radioactive measurement for the determination. In the case of the intramuscular administration of 14C-T-1220 to rats, about 92% of the radioactivity was excreted unchanged in urine and bile, but about 94% of the radioactivity in the feces was 14C-T-1220B. The same results were found in rats pretreated with SKF-525A and phenobarbital. In situ studies showed that 14C-T-1220 changed to 14C-T-1220B in the intestinal tracts, and in vitro studies showed that 14C-T-1220 changed to 14C-T-1220B in fecal homogenate. From these results, it seemed that 14C-T-1220 was changed to 14C-T-1220B by β-lactamase produced from intestinal flora.
- 著者
- 才川 勇 桃井 海秀 酒井 広志 高下 寛 大橋 俊則 南 尚 山本 芳子 福岡 義和
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.99, no.12, pp.1207-1218, 1979-12-25 (Released:2008-05-30)
- 参考文献数
- 16
- 被引用文献数
- 3 3
The stability, degradation pattern and structure of degradation products of sodium 7-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1551) in aqueous solution were investigated. T-1551 was kept in various solutions in pH and μ=0.5 at 35°, its degradation was followed by HPLC. T-1551 was stable at the range of pH 4.0-7.0, slightly unstable at acid and markedly unstable at alkaline. It was confirmed that in alkaline solution, 7-[D (-)-α-[3-[2-(N-ethyl-N-oxaloamino)-ethyl] ureido]-α-(4-hydroxyphenyl) acetamido]-3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid (T-1551A) was produced, and that in acidic solution, 7-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxy-methyl-3-cephem-4-carboxylic acid γ-lactone (T-1551B), 7-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid (T-1551C), 5-mercapto-1-methyl-1H-tetrazole (T-1551F), 2-[2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-2-(4-hydroxyphenyl) acetamido]-2-[1, 2, 5, 7-tetrahydro-7-oxo-4H-furo [3, 4-d] [1, 3] thiazin-2-yl] acetic acid (T-1551G), 2-[α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamidomethyl]-2, 3-dihydro-5-hydroxy-methyl-6H-thiazine-4-carboxylic acid γ-lactone (T-1551H) and N-formylmethyl-D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamide (T-1551D) were produced, respectively.
- 著者
- 才川 勇 桃井 海秀 酒井 広志 高下 寛 大橋 俊則 南 尚 山本 芳子 福岡 義和
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- 薬学雑誌 (ISSN:00316903)
- 巻号頁・発行日
- vol.99, no.12, pp.p1207-1218, 1979-12
The stability, degradation pattern and structure of degradation products of sodium 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1551) in aqueous solution were investigated. T-1551 was kept in various solutions in pH and μ=0.5 at 35°, its degradation was followed by HPLC. T-1551 was stable at the range of pH 4.0-7.0,slightly unstable at acid and markedly unstable at alkaline. It was confirmed that in alkaline solution, 7-[D (-)-α-[3-[2-(N-ethyl-N-oxaloamino)-ethyl] ureido]-α-(4-hydroxyphenyl) acetamido]-3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid (T-1551A) was produced, and that in acidic solution, 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxy-methyl-3-cephem-4-carboxylic acid γ-lactone (T-1551B), 7-[D (-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid (T-1551C), 5-mercapto-1-methyl-1H-tetrazole (T-1551F), 2-[2-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-2-(4-hydroxyphenyl) acetamido]-2-[1,2,5,7-tetrahydro-7-oxo-4H-furo [3,4-d] [1,3] thiazin-2-yl] acetic acid (T-1551G), 2-[α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamidomethyl]-2,3-dihydro-5-hydroxy-methyl-6H-thiazine-4-carboxylic acid γ-lactone (T-1551H) and N-formylmethyl-D-(-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamide (T-1551D) were produced, respectively.