AUTOXIDATION OF PYRIDOXALATED HEMOGLOBIN POLYOXYETHYLENE CONJUGATE

Hemoglobin-based therapeutics are currently in clinical trials in the United States and abroad as blood replacement solutions, nitric oxide scavengers, and radiation sensitizers. The potency of the therapeutics may be influenced by the oxidation state of the iron in the heme moie ty. The oxidation state is dependent upon the physical environment of the molecule and is influenced by parameters such as the chemical natu re of the hemoglobin therapeutic and its formulation. Pyridoxalated he moglobin polyoxyethylene conjugate (PHP) is one such compound currentl y in clinical trials in the U.S. for treatment of nitric oxide-depende nt, volume refractory shock. The autoxidation rates for PHP have been determined over a range of temperatures. The oxidation events were sho wn to be biphasic and were similar to those observed for purified huma n hemoglobin (HbAo). The initial fast oxidation events were modeled wi th first order rate constants at 37 degrees C and determined to be 0.0 22 hr(-1) and 0.025 hr(-1) for PHP and HbAo, respectively. The autoxid ation of PHP was shown to be independent of concentration from approxi mately 5 to 100 mg/mL. (C) 1998 Academic Press.