Soma Lawrence R, Uboh Cornelius E, Guan Fuyu, Luo Yi, Moate Peter J, Boston Raymond C, Driessen Bernd
*Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania; †Department of Chemistry, Pennsylvania Equine Toxicology & Research Center, West Chester University; and ‡Department of Anesthesiology, David Geffen School of Medicine, University of California-Los Angeles.
Anesth Analg. 2005 Jun;100(6):1570-1575. doi: 10.1213/01.ANE.0000154081.38466.09.
Hemoglobin-glutamer-200 (HBOC-200) is a hemoglobin (Hb)-based oxygen carrier (HBOC) comprising glutaraldehyde-polymerized bovine Hb. In this study, we sought to determine the pharmacokinetics of this first generation HBOC after IV infusion of 32.5 g of HBOC-200 solution in horses. Quantification of HBOC-200 in equine plasma and urine was performed using a method recently developed by our laboratory. The elimination from plasma was based on size distribution of the bovine Hb polymer. The decline of plasma concentration-time curve of HBOC-200 was described by a noninterchanging 2-compartmental model. The median elimination half-lives of the small and large aggregates were 1.3 and 12.0 h, respectively. Of the HBOC-200 infused, 47.0% was eliminated as the smaller molecular weight and 53% as the larger molecular weight polymers. The area under the plasma concentration-time curve was 5143.1 microg.h(-1).mL(-1). The volumes of distribution of the small and large aggregates were 86.9 and 63.9 mL/kg and the clearances were 42.1 and 3.8 mL.kg(-1).h(-1), respectively. In conclusion, elimination of first generation HBOCs was shown to be more complex than previously assumed because of the heterogeneous nature of these solutions. Mammalian species dispose of Hb using similar mechanisms, and there is no unique metabolic process in the horse that would not allow a logical extension of the general interpretation of this study.
血红蛋白-谷氨酰胺-200（HBOC-200）是一种基于血红蛋白（Hb）的氧载体（HBOC），由戊二醛聚合的牛血红蛋白组成。在本研究中，我们试图确定在给马静脉输注32.5 g HBOC-200溶液后，这种第一代HBOC的药代动力学。使用我们实验室最近开发的一种方法对马血浆和尿液中的HBOC-200进行定量。从血浆中的消除基于牛血红蛋白聚合物的大小分布。HBOC-200血浆浓度-时间曲线的下降用非交换性二室模型描述。小聚集体和大聚集体的中位消除半衰期分别为1.3小时和12.0小时。输注的HBOC-200中，47.0%以较小分子量聚合物的形式消除，53%以较大分子量聚合物的形式消除。血浆浓度-时间曲线下面积为5143.1μg·h⁻¹·mL⁻¹。小聚集体和大聚集体的分布容积分别为86.9 mL/kg和63.9 mL/kg，清除率分别为42.1 mL·kg⁻¹·h⁻¹和3.8 mL·kg⁻¹·h⁻¹。总之，由于这些溶液的异质性，第一代HBOC的消除比以前假设的更为复杂。哺乳动物物种使用类似的机制处理血红蛋白，马中不存在独特的代谢过程，因此本研究的一般解释可以合理地推广。
