SUPERPARAMAGNETIC IRON-OXIDE - PHARMACOKINETICS AND TOXICITY
SUPERPARAMAGNETIC IRON-OXIDE - PHARMACOKINETICS AND TOXICITY
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DOI：
10.2214/ajr.152.1.167
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发表时间：
1989-01-01
影响因子：
5
通讯作者：
LEWIS, J
中科院分区：
文献类型：
--
作者：
WEISSLEDER, R;STARK, DD;LEWIS, J
通过59 Fe放射性示踪研究、弛豫时间测量、逆转缺铁性贫血的能力、组织学检查和实验室参数，评价了目前用于临床试验的超顺磁性氧化铁制剂（AMI-25）的药代动力学（分布、代谢、生物利用度、排泄）和毒性（急性和亚急性毒性、致突变性）。对大鼠施用AMI-25（18 μ mol Fe/kg; 1 mg Fe/kg）后1小时，82.6 ± 0.001 μ mol Fe/kg。0.3%的给药剂量被隔离在肝脏中，6.2 ±.脾脏7.6%。59 Fe的峰值浓度在2小时后在肝脏和脾脏后4小时。59 Fe慢慢清除肝脏（半衰期，3天）和脾脏（半衰期，4天），并纳入血红蛋白的红细胞在一个时间依赖性的方式。T2对肝脏和脾脏的半衰期（24-48小时）短于59 Fe清除率，表明AMI-25代谢为其他形式的铁。AMI-25（30 mg Fe/kg）的IV给药纠正了缺铁性贫血，并在7天内显示出与市售IV铁制剂相似的生物利用度。通过在接受总共3000 μ mol Fe/kg的大鼠或比格犬中的组织学或血清学研究，未检测到急性或亚急性毒性作用，所述Fe/kg是用于肝脏MR成像的建议剂量的150倍。我们的研究结果表明，AMI-25是一种完全生物相容的潜在MR造影剂。
The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 .mu.mol Fe/kg; 1 mg Fe/kg), 82.6 .+-. 0.3% of the administered dose was sequestered in the liver and 6.2 .+-. 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 .mu.mol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.