Tsuchiya T, Ishibashi K, Terakawa M, Nishiyama M, Itoh N, Noguchi H
Eur J Drug Metab Pharmacokinet. 1982 Jan-Mar;7(1):59-64. doi: 10.1007/BF03189544.
The absorption, distribution, metabolism, and excretion of 3-(N-formylhydroxylamino) propylphosphonic acid monosodium salt (fosmidomycin), a new antibiotic, were investigated in rats and dogs after i.v. and oral dosing. After i.v. administration of 10 mg/kg of body weight, [14C]-fosmidomycin was excreted mainly in the urine (about 90% of dose within 72 h); and only a little was excreted in the expired air (14CO2) and bile of rats (less than 1% of dose), which suggested the absence of enterohepatic circulation. After oral administration of 10 mg/kg of body weight to rats, 34% and 61% of dose were excreted in the urine and faeces, respectively, suggesting about 30% gastro-intestinal absorption. No metabolites were found by autoradiography of the urine after thin layer chromatography. Radioactivity levels in the serum essentially agreed with the unchanged fosmidomycin levels determined by reverse isotope dilution method. [14C]-fosmidomycin was rapidly distributed in the tissues of rats, and was maintained in high concentration in the liver, kidneys, and bone. The serum level data after i.v. administration closely fitted a 3-compartment open model with first order kinetics after nonlinear least squares regression by NONLIN. The half-lives of the serum level curves for the early, midway, and terminal phases were: 0.13, 0.51, and 17.3 h, respectively in rats; and 0.44, 0.75, and 2.0 h, respectively in dogs.
对新型抗生素3 -（N - 甲酰羟氨基）丙基膦酸单钠盐（磷霉素氨丁三醇）在大鼠和犬静脉注射及口服给药后的吸收、分布、代谢和排泄情况进行了研究。静脉注射10mg/kg体重的[¹⁴C] - 磷霉素氨丁三醇后，主要经尿液排泄（72小时内约占给药剂量的90%）；只有少量经大鼠呼出气体（¹⁴CO₂）和胆汁排泄（少于给药剂量的1%），这表明不存在肠肝循环。给大鼠口服10mg/kg体重后，分别有34%和61%的给药剂量经尿液和粪便排泄，提示胃肠道吸收约为30%。薄层色谱法对尿液进行放射自显影未发现代谢产物。血清中的放射性水平与用反向同位素稀释法测定的未变化的磷霉素氨丁三醇水平基本一致。[¹⁴C] - 磷霉素氨丁三醇在大鼠组织中迅速分布，并在肝脏、肾脏和骨骼中保持高浓度。静脉注射后的血清水平数据经NONLIN非线性最小二乘回归后，紧密拟合三室开放模型及一级动力学。大鼠血清水平曲线早期、中期和终末期的半衰期分别为：0.13、0.51和17.3小时；犬分别为0.44、0.75和2.0小时。
