- 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.