Pharmacokinetics of ¹²⁵I-radiolabelled PEG-hemoglobin SB1

Abstract

PEG-hemoglobin SB1 (SB1) is a polyethylene glycol (PEG)-modified hemoglobin-based oxygen carrier, intended for use as resuscitation fluid for brain stroke and as a blood substitute. An intravenous pharmacokinetics (PK) studies with SB1 was investigated in male albino Sprague-Dawley (SD) rats and male beagle dogs at doses of 5 and 12.5 ml/kg for rats and 10 ml/kg for dogs. Total hemoglobin in plasma and whole blood was determined by gamma scintillation counter–detecting ¹²⁵I-radiolabelled SB1. In the 5 ml/kg rats (n = 9), the C_max, t_1/2, AUC_t and T_max were 9.055 mg equivalents/ml, 9.6 hr, 79.6 mg equivalents.hr/ml and 0.20 hr in the plasma and 4.954 mg equivalents/ml, 9.7 hr, 37.6 mg equivalents.hr/ml and 0.11 hr in the whole blood, respectively. Those parameters in the 12.5 ml/Kg of rats (n = 9) were 19.00 mg equivalents/ml, 10.6 hr, 223.5 mg equivalents.hr/ml and 0.33 hr in the plasma and 10.58 mg equivalents/ml, 16.1 hr, 99.0 mg equivalents.hr/ml and 0.33 hr in the whole blood, respectively. An increase in the dose level from 5 to 12.5 ml/kg resulted in the increase in both C_max and AUC₂₄, and the increases in these parameters appeared to be in proportion to the dose increment. Thus, following the 2.5-fold increase in administered dose, C_max was increased by a factor of 2.1 in both plasma and whole blood, while AUC₂₄ was increased by a factor of 2.8 for plasma and 2.6 for whole blood. In the dogs receiving 10 ml/kg (n = 3), the C_max, t_1/2, AUC₁₆₈ and T_max were 12.70 mg equivalents/ml, 47.2 hr, 425.7 mg equivalents.hr/ml and 0.083 hr in the plasma and 8.372 mg equivalents/ml, 50.3 hr, 241.3 mg equivalents.hr/ml and 1.003 hr in the whole blood, respectively. The present work provides an insight into the pharmacological behavior of a PEG-modified hemoglobin.

Keywords:

• PEG-hemoglobin SB1
• Stroke
• Oxygen carrier
• Blood substitute
• Pharmacokinetics
• Beagle dog
• SD rat