Pharmacokinetics of hemoglobin-based oxygen carrier hemoglobin-glutamer-200 bovine (oxyglobin) in the horse |
| |
| Authors: | LR Soma F Guan CE Uboh Y Luo PJ Moate B Driessen |
| |
| Institution: | University of Pennsylvania, Kennett Square, PA, USA; West Chester University, West Chester, PA, USA |
| |
| Abstract: | Oxyglobin (OXY) is a hemoglobin‐based oxygen carrier (HBOC) made of glutaraldehyde‐polymerized bovine hemoglobin (bHb). Products similar to OXY are under development for use as temporary blood substitutes in trauma, shock and anemia. Since they all may increase blood O2‐carrying capacity and thus, possibly tissue oxygenation, they may also be used to enhance performance of both equine and human athletes. That is why HBOCs are banned from use in athletic competition. Our goal was to determine the pharmacokinetics of OXY after intravenous (IV) infusion to horses. Blood and urine samples were collected from adult horses that received an IV dose of 32.5 g of OXY. Concentrations of OXY in plasma and urine were quantified using a newly developed LC/Q‐TOF‐MS/MS detection technique. Level of quantification (LOQ) was 50 μg mL–1. The decline of the plasma concentration‐time curve of the HBOC was described by a 2‐compartment model (C1 and C2). The median distribution alpha (t1/2k1,0) and elimination beta (t1/2k2,0) half‐lives were 1.3 and 12.0 hours, respectively. The bHb molecules in OXY are not of uniform size and vary substantially in molecular weight (MW). Of the OXY molecules 53% were eliminated in C1, which represented the smaller MW molecules and 47% in C2, which represented the larger MW bHb. The maximal 0‐time plasma concentration was 662.0 μg/mL and declined to 97.1 μg mL–1 at 24 h. The area below the plasma concentration‐time curve was 5143 μg h–1 mL–1. The volumes of C1 and C2 were 86.9 and 63.9 mL kg–1, respectively. Oxyglobin was not detected in urine. This study shows the detection and quantification in equine plasma of a HBOC following IV infusion and demonstrates the short half‐life of about 50% of infused bHb molecules. |
| |
| Keywords: | |
|
|
