Fisher E A, McLachlan D R, Kruck T P, Mustard R A
Department of Physiology, University of Toronto, Ont., Canada.
Pharmacology. 1990;41(5):263-71. doi: 10.1159/000138730.
Desferrioxamine (DFO) metabolism and its pharmacokinetics were studied in a swine model using high-performance liquid chromatography. DFO and three iron-binding metabolites occurred in plasma. Interindividual differences in pharmacokinetics and metabolism were observed. Urine analysis in 4 pigs showed three iron-binding metabolites. The mean percent dose excreted in urine in the form of the parent drug was 45 +/- 10% and 10 +/- 2% (means +/- SD) in the form of metabolites. Of the total amount of the parent drug infused, 3 h after initiation, 87% was in the form of DFO, whereas 13% was present as the DFO-iron III complex which represented 45 mg of urinary iron elimination. The described DFO infusion protocol provides for sufficient DFO to chelate significant amounts of ferric iron in excess of normal levels, thus allowing experimental studies of iron chelation in a variety of disease states.
使用高效液相色谱法在猪模型中研究了去铁胺(DFO)的代谢及其药代动力学。血浆中出现了DFO和三种铁结合代谢物。观察到药代动力学和代谢存在个体差异。对4头猪的尿液分析显示有三种铁结合代谢物。以母体药物形式经尿液排泄的平均剂量百分比为45±10%,以代谢物形式排泄的平均剂量百分比为10±2%(均值±标准差)。在开始输注后3小时,输注的母体药物总量中,87%为DFO形式,而13%以DFO-铁III复合物形式存在,该复合物代表45毫克尿铁清除量。所描述的DFO输注方案可提供足够的DFO,以螯合大量超过正常水平的三价铁,从而允许在各种疾病状态下进行铁螯合的实验研究。