1983 年 103 巻 4 号 p. 414-425
Metabolism of sodium 7β-[(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylate (T-1982), a new β-lactam antibiotic, was studied in vitro and in vivo. When T-1982 was administered intravenously to various animals, the bioautogram of their urine samples showed that T-1982 existed in quantity, but 7β-[(2R, 3S)-2-[3-[2-(N-ethyl-N-oxaloamino)ethyl]ureido]-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (T-1982A) and 7α-methoxy-7β-[(5-methyl-2-oxooxazolidin-4-yl)carboxamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (T-1982 B) existed slightly. Similarly, T-1982A and T-1982B as metabolites of T-1982 were detected in the urine, bile and feces of various animals by high pressure liquid chromatography (HPLC). After the intravenous administration of 14C-T-1982 to rat and mouse, 14C-radioactivity excreted in the urine, bile and feces was measured with HPLC and radioassay. As a result, 92.2-98.1% of each collected radioactivity was 14C-T-1982, 0.5-2.6% was 14C-T-1982A and 1.1-3.8% was 14C-T-1982B. The degradation rate of T-1982 during the incubation with the homogenates of various rat's organs was similar to that in 0.1 M P.B. (pH 7.0), therefore it seemed that T-1982 was not degraded by enzymes from various organs. 1-Ethyl-2, 3-dioxopiperazine (T-1982C) was assumed to be produced in company with the production of T-1982B. Further T-1982A and T-1982B were administered to rabbits, and 14C-T-1982C was administered to rat. Plasma levels of these compounds disappeared immediately. When T-1982 was administered intravenously to volunteers, T-1982A and T-1982B were detected in their urine as seen in the urine of various animals. It was considered that the metabolism of T-1982 in human was the same as that in these animals.
