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 moiety. The oxidation state is dependent upon the physical environment of the molecule and is influenced by parameters such as the chemical nature of the hemoglobin therapeutic and its formulation. Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) is one such compound currently in clinical trials in the U.S. for treatment of nitric oxide-dependent, volume refractory shock. The autoxidation rates for PHP have been determined over a range of temperatures. The oxidation events were shown to be biphasic and were similar to those observed for purified human hemoglobin (HbAo). The initial fast oxidation events were modeled with first order rate constants at 37 degrees C and determined to be 0.022 hr(-1) and 0.025 hr(-1) for PHP and HbAo, respectively. The autoxidation of PHP was shown to be independent of concentration from approximately 5 to 100 mg/mL. (C) 1998 Academic Press.