Comparative Pharmacokinetics of a Hemoglobin-based Oxygen Carrier

Expectations and Implications of Blood Sparing with Hemoglobin Based Oxygen Carriers

“…With regard to more specific assumptions, the modeling of HBOC vascular pharmacokinetics as an exponential decay is consistent with the empirical observations made for some, but not all, hemoglobin solutions infused into animals and humans [8][9][10][11][12][13][14]. For the purposes of this exercise the HBOC half-life is taken to be the half-life of functional hemoglobin in the circulation.…”

“…Oxidation of hemoglobin to the inactive met form is observed after infusion into mammals [13,15], but this process does not appear to have a profound impact on the assumption of exponential decay kinetics, but rather results in an effective decrease in the functional half-life relative to the circulating half-life of plasma hemoglobin. The range of HBOC half-lives chosen for evaluation in this exercise encompasses the range of values reported in the literature for the current generation of HBOC solutions in humans and large animals [10,[13][14][15][16].…”

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

“…Polymerization further increases half-life (Tam et al 1978, DeVenuto and Zegna 1983, Keipert and Chang 1983, Sehgal et al 1984, Keipert and Chang 1987, Snyder et al 1987, Berbers et al 1991, Lenz et al 1991, Hsia et al 1993, Bakker et al 1993, Anderson et al 1993, Lee et al 1995, Pearce et al 2003, Wicks et al 2003, Bonegio et al 2006, Buehler et al 2010, Baek et al 2012, Elmer et al 2012. Most reported values have not been corrected for blood volume changes, but the increased half-life of crosslinked and/or polymerized HBOCs relative to unmodifi ed Hb is not an artifact of such changes because these modifi cations do not increase the oncotic pressure at a given Hb concentration (DeVenuto 1983, Sehgal et al 1984, Berbers et al 1991).…”

“…Chang 1987, Hess et al 1989, Keipert et al 1989a, Hughes et al 1996, Przybelski et al 1996, Viele et al 1997, Carmichael et al 2000, Pearce et al 2003 in both animals and humans (Figures 1 and 2). Th e eff ect is modest with unmodifi ed Hbs, but more pronounced with crosslinked and polymerized HBOCs , Keipert 1992.…”

“…A third trend is the variation in circulatory persistence with species (Hess et al 1989, Pearce et al 2003. While the nature and relative paucity of comparable data do not permit a rigorous statistical analysis, two qualitative conclusions seem warranted.…”