Biomedical subjects
Publications and source records attributed to F Shono.
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Among several intracellular protease tested, cathepsin H transformed leukotriene D4 to E4 with a release of glycine in a stoichiometric quantity. Under the optimal conditions the rate of leukotriene D4 transformation by cathepsin H was about 3% of the hydrolysis rate of alpha-N-benzoyl-DL-arginine-2-naphthylamide which is commonly utilized as a very efficient substrate to test the peptidase activity of the enzyme. Leukotriene C4 was not transformed to leukotriene D4 by cathepsin H. Neither cathepsin B nor C was active with leukotrienes C4 and D4.
A sensitive and reliable high-pressure liquid chromatography (HPLC) assay for miloxacin and its two principal metabolites, 5,8-dihydro-8-oxo-2H-1,3-dioxolo[4,5-g]quinoline-7-carboxylic acid (M-1) and 1,4-dihydro-1,6-dimethoxy-7-hydroxy-4-oxoquinoline-3-carboxylic acid (M-2), in human serum and urine was developed. A strong anion-exchange Zipax SAX column using a mobile phase of 0.01 M citric acid solution containing 0.03 M sodium nitrate with pH 5.0 was used to achieve separation of the three compounds. The retention times of miloxacin, M-1, and M-2 were 3.8, 9.3, and 5.9 min, respectively. Serum and urine concentrations of these compounds as low as 10 ng/ml were measured. When results from the HPLC assay were compared with those from the microbiological assay of serum and urine samples from human subjects receiving miloxacin orally, the correlation coefficients were 0.94 for the serum and 0.99 for the urine. The HPLC assay method presents an alternative to the microbiological assay and permits future pharmacokinetic investigations of miloxacin.
Absorption, distribution, excretion, and metabolism of 5,8-dihydro-5-methoxy-8-oxo-2H-1, 3-dioxolo[4,5-g]quinoline-7-carboxylic acid(miloxacin), a new antimicrobial agent, were studied in female rats by using 14C-miloxacin which was administered orally to the animals in a dose of 50 mg/kg. 14C-Miloxacin was absorbed rather fast and the radioactivity of 14C distributed widely in a variety of tissues. Peak concentrations of 14C in serum and tissues occurred 1 to 2 hr after dosing, and were approximately 60 micrograms equivalent of miloxacin per ml or g in serum, liver and kidney. Excretion of 14C in urine and feces was fast, and recoveries of 14C during 48 hr period were approximately 30% in urine and 60% in feces. Concentrations of intact 14C-miloxacin were higher in serum and kidney while lower in liver. Major metabolites in excreta were the demethoxy derivative (M-1) and the glucuronide of miloxacin; and as minor metabolites five other metabolites were identified. As sex differences, the following facts were observed; concentrations of 14C in serum and tissues were generally 1.2 to 1.6 times higher in female rats those in male rats, and the capacity to metabolize miloxacin, especially in the glucuronic acid conjugation, was rather lower in female rats than that in male rats.
Isolation and characterization of metabolites of miloxacin, a new antimicrobial agent, were undertaken with rats. 14C-Miloxacin was orally administered to Sprague-Dawley rats at a dose of 50 mg/kg, and urine, bile and feces were collected. The metabolites extracted from the biological samples were isolated by column and thin-layer chromatographies. Characterization of the isolated metabolites was carried out by comparison with the authentic materials in various physicochemical analyses. Eight metabolites together with intact miloxacin were identified; containing the metabolites of N-demethoxy (M-1), catechol (M-3) and 6-methoxy (M-2 and M-4) types and their conjugates with glucuronic acid.
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