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Anesthesia and analgesia2005; 100(6); 1570-1575; doi: 10.1213/01.ANE.0000154081.38466.09

The pharmacokinetics of hemoglobin-based oxygen carrier hemoglobin glutamer-200 bovine in the horse.

Abstract: 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.
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Publication Date: 2005-05-28 PubMed ID: 15920176DOI: 10.1213/01.ANE.0000154081.38466.09Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the pharmacokinetics, or the movement within the body, of an oxygen-carrying protein, Hemoglobin-glutamer-200 (HBOC-200), after being intravenously administered in horses. The researchers explore how this substance is distributed and eliminated from the horse’s system.

What is Hemoglobin-glutamer-200 (HBOC-200)?

  • HBOC-200 is a type of protein designed to carry oxygen throughout the body, which is produced using glutaraldehyde-polymerized bovine hemoglobin (Hb).
  • This compound belongs to a class of substances known as hemoglobin-based oxygen carriers (HBOCs). These are intended to act as substitutes for red blood cells, especially in situations like blood transfusions.

Methodology of the Study

  • The researchers administered an intravenous (IV) infusion of 32.5 g of HBOC-200 solution in horses and observed its distribution and elimination.
  • The detection of HBOC-200 in horse plasma and urine was carried out using a technique recently developed by the research team.
  • The researchers developed a noninterchanging 2-compartmental model to describe the declining concentration of HBOC-200 over time in the plasma.

Findings of the Study

  • The investigation found that the half-life (the time taken for the concentration to reduce by half) of the smaller and larger aggregates of HBOC-200 were 1.3 and 12 hours, respectively.
  • The researchers discovered that 47% of the HBOC-200 infused was eliminated as smaller molecular weight polymers, and 53% as larger molecular weight polymers.
  • The research team also calculated the volume of distribution of the small and large aggregates and their clearances from the horse’s body.
  • The study highlighted that the elimination of first-generation HBOCs proved to be more complex than initially thought due to the heterogeneous nature of these solutions.

Conclusion and Implications of the Study

  • It was concluded that various mammalian species (including horses) dispose of hemoglobin using similar mechanisms. As such, there is no unique metabolic process exclusive to horses that could challenge the general interpretation derived from this study.
  • The findings could have significant implications for the use of HBOCs in blood transfusions and other medical applications, suggesting that the body’s processes for handling these substances are more complex than previously thought.

Cite This Article

APA
Soma LR, Uboh CE, Guan F, Luo Y, Moate PJ, Boston RC, Driessen B. (2005). The pharmacokinetics of hemoglobin-based oxygen carrier hemoglobin glutamer-200 bovine in the horse. Anesth Analg, 100(6), 1570-1575. https://doi.org/10.1213/01.ANE.0000154081.38466.09

Publication

Anesthesia and analgesia
ISSN: 0003-2999
NlmUniqueID: 1310650
Country: United States
Language: English
Volume: 100
Issue: 6
Pages: 1570-1575

Researcher Affiliations

Soma, Lawrence R
  • *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.
Uboh, Cornelius E
    Guan, Fuyu
      Luo, Yi
        Moate, Peter J
          Boston, Raymond C
            Driessen, Bernd

              MeSH Terms

              • Algorithms
              • Animals
              • Area Under Curve
              • Blood Substitutes / administration & dosage
              • Blood Substitutes / pharmacokinetics
              • Cattle
              • Female
              • Half-Life
              • Hemoglobins / analysis
              • Horses / physiology
              • Infusions, Intravenous
              • Male
              • Models, Biological
              • Oxygen / blood

              References

              This article includes 23 references
              1. Winslow RM. New transfusion strategies: red cell substitutes.. Annu Rev Med 1999;50:337–53.
              2. Driessen B, Jahr JS, Lurie F. Arterial oxygenation and oxygen delivery after hemoglobin-based oxygen carrier infusion in canine hypovolemic shock: a dose-response study.. Crit Care Med 2003;31:1771–9.
              3. Schumacher YO, Schmid A, Dinkelmann S. Artificial oxygen carriers: the new doping threat in endurance sport?. Int J Sports Med 2001;22:566–71.
              4. Haney CR, Buehler PW, Gulati A. Purification and chemical modifications of hemoglobin in developing hemoglobin based oxygen carriers.. Adv Drug Deliv Rev 2000;40:153–69.
              5. Guan F, Uboh CE, Soma LR. Confirmation and quantification of hemoglobin-based, oxygen carriers in equine and human plasma by liquid chromatography tandem mass spectrometry.. Anal Chem 2004;76:5127–35.
              6. Guan F, Uboh CE, Soma LR. Unique tryptic peptides specific for bovine and human hemoglobin in the detection and confirmation of hemoglobin-based oxygen carrier.. Anal Chem 2004;76:5118–26.
              7. Stefanovski D, Moate PJ, Boston C. WinSAAM: a windows based compartmental modeling system.. J Metab 2003;52:1153–66.
              8. Varlet-Marie E, Ashenden M, Lasne F. Detection of hemoglobin-based oxygen carriers in human serum for doping analysis: confirmation by size-exclusion HPLC.. Clin Chem 2004;50:723–31.
              9. Thevis M, Ogorzalek Loo RR, Loo JA, Schanzer W. Doping control analysis of bovine hemoglobin-based oxygen therapeutics in human plasma by LC-electrospray ionization-MS/MS.. Anal Chem 2003;75:2955–61.
              10. Hsia JC, Song DL, Er SS. Pharmacokinetic studies in the rat on a o-raffinose polymerized human hemoglobin.. Biomater Artif Cells Immobilization Biotechnol 1992;20:587–95.
              11. Hughes GS Jr, Antal EJ, Locker PK. Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans.. Crit Care Med 1996;24:756–64.
              12. Keipert PE, Gomez CL, Gonzales A. The role of the kidneys in the excretion of chemically modified hemoglobins.. Biomater Artif Cells Immobilization Biotechnol 1992;20:737–45.
              13. Malchesky PS, Takahashi T, Iwasaki K. Conjugated human hemoglobin as a physiological oxygen carrier: pyridoxalated hemoglobin polyoxyethylene conjugate (PHP).. Int J Artif Organs 1990;13:442–50.
              14. Palaparthy R, Kastrissios H, Gulati A. Pharmacokinetics of diaspirin cross-linked haemoglobin in a rat model of hepatic cirrhosis.. J Pharm Pharmacol 2001;53:179–85.
              15. Vandegriff KD, Malavalli A, Wooldridge J. MP4, a new nonvasoactive PEG-Hb conjugate.. Transfusion 2003;43:509–16.
              16. Rippe B, Haraldsson B. Transport of macromolecules across microvascular walls: the two-pore theory.. Physiol Rev 1994;74:163–219.
              17. Conhaim RL, Cooler SD, McGrath AM. Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph.. Am J Respir Crit Care Med 1998;158:1204–12.
              18. Conhaim RL, Rodenkirch LA, Watson KE, Harms BA. Acellular hemoglobin solution enters compressed lung capillaries more readily than red blood cells.. J Appl Physiol 2000;89:1198–204.
              19. Matheson B, Kwansa HE, Bucci E. Vascular response to infusions of a nonextravasating hemoglobin polymer.. J Appl Physiol 2002;93:1479–86.
              20. Keipert PE, Gomez CL, Gonzales A. Diaspirin cross-linked hemoglobin: tissue distribution and long-term excretion after exchange transfusion.. J Lab Clin Med 1994;123:701–11.
              21. Naylor JR, Bayly WM, Schott HC 2nd. Equine plasma and blood volumes decrease with dehydration but subsequently increase with exercise.. J Appl Physiol 1993;75:1002–8.
              22. Muir WW, Kohn CW, Sams R. Effects of furosemide on plasma volume and extracellular fluid volume in horses.. Am J Vet Res 1978;39:1688–91.
              23. Treib J, Baron JF, Grauer MT, Strauss RG. An international view of hydroxyethyl starches.. Intensive Care Med 1999;25:258–68.

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