Merali S, Chin K, Del Angel L, Grady R W, Armstrong M, Clarkson A B
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York 10016, USA.
Antimicrob Agents Chemother. 1995 Sep;39(9):2023-6. doi: 10.1128/AAC.39.9.2023.
The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO.
铁螯合剂去铁胺（DFO）已被证明在卡氏肺孢子虫肺炎（PCP）动物模型中具有活性，在小鼠和大鼠模型中，每日有效的腹腔推注剂量分别为400和1000 mg甲磺酸去铁胺/千克体重。连续输注在大鼠模型中产生了适度改善的反应。此处报告的数据表明，在大鼠模型中，以每日195和335 mg甲磺酸去铁胺/千克体重连续输注所达到的反应，分别与血浆中1.3和2.5微克去铁胺/毫升的平均浓度以及肺组织中4.9和6.0微克去铁胺/克肺组织的平均浓度相关。由于目前临床使用甲磺酸去铁胺治疗铁过载会使患者血浆中产生更高的浓度，去铁胺可能被证明是一种有用的抗PCP治疗药物。与血浆中观察到的浓度相比，在肺组织中观察到的去铁胺浓度高2.4至3.8倍，这可能对PCP对去铁胺的反应很重要。
