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 iro n metabolism and pharmacokinetics of hemoglobin-based oxygen carrier-2 01 (HBOC-201), a polymerized hemoglobin product of bovine origin. A ra ndomized, single-blind, single-dose study design was used, The study w as performed at the Upjohn Research Clinics in Kalamazoo, Michigan. Fo ur 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 (appro ximate to 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 m i) or control solution (Ringer's lactate). Serial arterial blood gas s amples with a radial artery catheter and simultaneous pulse oximetry w ere done during the first 24 hours. Serial samples for serum iron, fer ritin, 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 hour s 8 (up to 220 mu g/dl) and 48 (up to 180 ng/ml), respectively. Serum iron levels paralleled HBOC-201 concentrations. Plasma half-life of HB OC-201 was about 20 hours. Serum erythropoietin increased by twofold t o 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 i n men and women.