Hematologic effects of a novel hemoglobin-based oxygen carrier in normal male and female subjects.
The objective of this study was to assess the relationship between iron metabolism and pharmacokinetics of hemoglobin-based oxygen carrier-201 (HBOC-201), a polymerized hemoglobin product of bovine origin. A randomized, single-blind, single-dose study design was used. The study was performed at the Upjohn Research Clinics in Kalamazoo, Michigan. Four groups of healthy men and women (n = 24), who either received HBOC-201 (9 men, 9 women) or a control solution (Ringer's lactate) (3 men, 3 women) participated in the study. All subjects had phlebotomy (approximately 15% blood volume) followed by 3:1 hemodilution with Ringer's lactate and an intravenous infusion of HBOC-201 (up to 45 gm or 350 ml) or control solution (Ringer's lactate). Serial arterial blood gas samples with a radial artery catheter and simultaneous pulse oximetry were done during the first 24 hours. Serial samples for serum iron, ferritin, erythropoietin, and plasma HBOC-201 levels were taken over a 1-month period. In the HBOC-201-treated groups, serum iron and ferritin levels increased. Peak serum iron and ferritin levels occurred by hours 8 (up to 220 micrograms/dl) and 48 (up to 180 ng/ml), respectively. Serum iron levels paralleled HBOC-201 concentrations. Plasma half-life of HBOC-201 was about 20 hours. Serum erythropoietin increased by twofold to sixfold over baseline (p < 0.001) at 24 hours. No urinary hemoglobin was detected in the groups with HBOC-201-treated subjects. This study demonstrates that HBOC-201 produces increases in serum iron, ferritin, and erythropoietin that closely parallel plasma levels of HBOC-201 in men and women.
Hughes
G S
GS
Department of Clinical Development I, Upjohn Company, Kalamazoo, MI 49001, USA.
Francome
S F
SF
Antal
E J
EJ
Adams
W J
WJ
Locker
P K
PK
Yancey
E P
EP
Jacobs
E E
EE
D000328:Adult; D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D001784:Blood Gas Analysis; D001802:Blood Substitutes / Q000493:pharmacokinetics / Q000494:pharmacology*; D001803:Blood Transfusion; D002417:Cattle; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000097:blood; D006400:Hematocrit; D006438:Hemodilution; D006454:Hemoglobins / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D018962:Phlebotomy; D016037:Single-Blind Method
D001802:Blood Substitutes; D006454:Hemoglobins; D004921:Erythropoietin; C096798:HBOC 201; D005293:Ferritins; D007501:Iron; D010100:Oxygen