Pharmacokinetics of 125I-radiolabelled PEG-hemoglobin SB1.
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 Cmax, t1/2, AUCt and Tmax 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 Cmax 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, Cmax 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 Cmax, t1/2, AUC168 and Tmax 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.
Lee
Jiwon
J
SunBio Inc., Anyang City, South Korea.
Lee
Junhee
J
Yoon
Sojung
S
Nho
Kwang
K
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs; D006454:Hemoglobins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012588:Scintillation Counting
D001802:Blood Substitutes; D006454:Hemoglobins; D007457:Iodine Radioisotopes; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols