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

Figures & data

Figure 1. Circulating half-life of HBOCs in rats as a function of dose: unmodified Hb (♦), crosslinked tetrameric Hb (■), NFPLP-crosslinked, glutaraldehyde-polymerized Hb (▲), glutaraldehyde-polymerized bovine Hb (x). Data from (Bleeker et al. 1986, Snyder et al. 1987, Keipert et al. 1989b, Bleeker et al. 1992, Keipert et al. 1993, Keipert et al. 1994, Migita et al. 1997, Pearce et al. 2003).

Figure 2. Circulating half-life of HBOCs in humans as a function of dose: crosslinked tetrameric human Hb (♦), raffinose-polymerized human Hb (■), glutaraldehyde-polymerized bovine Hb (▲), recombinant crosslinked tetrameric human Hb (x). Data from (Hughes et al. 1995, Hughes et al. 1996, Przybelski et al. 1996, Viele et al. 1997, Carmichael et al. 2000).

Figure 3. Circulating half-life of HBOCs in animals as a function of molecular weight: raffinose-polymerized human Hb—50% exchange transfusion in rats (♦), NFPLP-crosslinked and glutaraldehyde-polymerized human Hb—35% exchange transfusion in rats (■), NFPLP-crosslinked and glutaraldehyde-polymerized human Hb—50% exchange transfusion in rats (x), NFPLP-crosslinked and glutaraldehyde-polymerized human Hb—70% exchange transfusion in rats (▲), glutaraldehyde-polymerized bovine Hb—3 g/kg in guinea pigs (⋇). Data from (Berbers et al. 1991, Bleeker et al. 1992, Hsia et al. 1993, Baek et al. 2012).

Figure 4. Comparison of intravascular half-life of two HBOCs in human and non-human species at 0.6–1.6 g/kg doses: crosslinked tetrameric Hb (■), glutaraldehyde-polymerized bovine Hb (□). Data from (Snyder et al. 1987, Hess et al. 1989, Hughes et al. 1995, Migita et al. 1997, O’Hara et al. 2001, Pearce et al. 2003).

Table I. Comparison of Total and Functional Half-Lives of HBOCs.^a

HBOC Type	Test Species	T1/2 Total HBOC (h)	T1/2 Functional HBOC (h)
Human dextran-coupled	Dog	58	46
bovine glutaraldehyde-polymerized	Guinea Pig	11.1	6.9
”	”	7.3	5.6
Bovine glutaraldehyde-polymerized	Rat	15.6	13.4
”	Guinea Pig	15.7	12.9
Bovine glutaraldehyde-polymerized	Sheep	53	30
Bovine PEG-derivatized	Rat	17.7	15.6

^aData from (Tam et al. 1978, Lee et al. 1995, Conover et al. 1997b, Buehler et al. 2007, Buehler et al. 2010).

Figure 5. Identified and hypothetical routes of elimination of HBOC from plasma.

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