Pharmacokinetics of single and repeated injection of hemoglobin-vesicles in hemorrhagic shock rat model
Pharmacokinetics of single and repeated injection of hemoglobin-vesicles in hemorrhagic shock rat model
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DOI：
10.1016/j.jconrel.2009.02.009
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发表时间：
2009-06-19
影响因子：
10.8
通讯作者：
Otagiri, Masaki
中科院分区：
文献类型：
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作者：
Taguchi, Kazuaki;Maruyama, Toru;Otagiri, Masaki
血红蛋白-囊泡(HBVs)是一种脂质体人工氧气载体，在失血性休克(HS)时可用作复苏液体。众所周知，脂质体的药代动力学特性会随着病理条件和重复给药的改变而改变。因此，我们比较了HS期间单次和多次服用乙肝病毒的药代动力学。停用40%的血建立HS模型。正常组(非HS组)和HS1组注射I-125标记的乙肝病毒(I-125-乙肝病毒)。HS2组用未标记的乙肝病毒复苏，1h后注射I-125-HBV1。HS1大鼠的半衰期较短，但在第二次注射HBV后恢复到非HS水平。在给药后12h内，HS1组的组织分布最大，而HS2组在随后的时间点的组织分布最大。尿中排泄是主要的排泄途径，在非HS组和HS1组之间没有差异，但在HS2组显著减少。此外，使用异速生长方程估计人类体内乙肝病毒的半衰期约为3-4天。根据乙肝病毒的药代动力学，提示乙肝病毒可能是HS中有用的人工氧载体。(C)2009爱思唯尔B.V.保留所有权利。
Hemoglobin-vesicles (HbV) are liposomal artificial oxygen carriers that may be useful as a resuscitation fluid during hemorrhagic shock (HS). It is well-known that the pharmacokinetic properties of liposome change in response to both pathological conditions and repeated administration. Therefore, we compared the pharmacokinetics of single versus repeated administration of HbV during HS. HS was induced by withdrawal of 40% of total blood volume. The normal (non-HS) and HS1 group was received an injection of I-125-labeled HbV (I-125-HbV). The HS2 group was resuscitated with non-labeled HbV, and 1 h later, it received an injection of I-125-HbV. The half-life was shorter in HS1 rats, but it returned to non-HS levels after the second HbV injection. During 12 h after administration of HbV, tissue distribution of HbV was greatest in the HS1 group; however, the HS2 group had the greatest tissue distribution at subsequent time points. Excretion into urine, major elimination pathway, did not differ between non-HS and HS1 rats, but was significantly reduced in the HS2 group. Furthermore, the half-life of HbV in humans was estimated to be approximately 3-4 days using an allometric equation. This suggests that HbV may be a useful artificial oxygen carrier in HS based on HbV pharmacokinetics. (C) 2009 Elsevier B.V. All rights reserved.