Pharmacokinetics and mechanisms of plasma removal of hemoglobin-based oxygen carriers

川地163 化学 血红蛋白 药代动力学 单核吞噬细胞系统 脾脏 药理学 受体 巨噬细胞 生物化学 内科学 免疫学 生物 医学 体外
作者
Timothy N. Estep
出处
期刊:Artificial Cells Nanomedicine and Biotechnology [Informa]
卷期号:43 (3): 203-215 被引量:9
标识
DOI:10.3109/21691401.2015.1047501
摘要

The circulatory persistence, distribution, and metabolism of hemoglobin-based oxygen carriers (HBOCs) is a major determinant of their safety and efficacy. In this communication, published data on the pharmacokinetics and routes of plasma elimination of HBOCs are summarized and evaluated. The circulating half-life of HBOCs is dose-dependent in both animals and humans. Half-life also increases with molecular weight in animals, at least up to the MDa range. The functional half-life of HBOCs is diminished by as much as 40% due to oxidation of the heme group relative to the overall rate of removal of hemoglobin (Hb) from plasma. Kidney excretion of HBOCs is greatly diminished compared to that of unmodified Hb, but the liver remains a primary site of catabolism. Both hepatocytes and Kupffer cells have been implicated in receptor-mediated HBOC uptake. Removal also occurs in the spleen and/or bone marrow and probably at dispersed sites in the endothelium as well. HBOCs extravasate into the lymph at a rate inversely proportional to their molecular weight and are taken up by monocyte/macrophage CD163 receptors, both as free Hb and in complexes with haptoglobin (Hp). The interactions with both Hp and the CD163 receptor are altered by Hb modification. However, monocyte/macrophage uptake may not be a quantitatively important route for the removal of clinically relevant doses of HBOCs. The relative contributions of different removal pathways have yet to be comprehensively determined, particularly in humans.
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