Toxicology and Safety Determination for a Novel Therapeutic Dual Carbon Monoxide and Oxygen Delivery Agent
- *Corresponding Author:
- Hemant Misra, Ph.D
Prolong Pharmaceuticals LLC
300B Corporate Court, South Plainfield
NJ 07080, USA
E-mail: [email protected]
Received Date: May 22, 2014; Accepted Date: July 09, 2014; Published Date: July 14, 2014
Citation: Misra H, Kazo F, Newmark JA (2014) Toxicology and Safety Determination for a Novel Therapeutic Dual Carbon Monoxide and Oxygen Delivery Agent. J Clin Toxicol 4:205. doi: 10.4172/2161-0495.1000206
Copyright: 2014 Misra H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Conditions in patients with hemoglobinopathies are far more complex and variable than in healthy humans due to the cascade of injury from hypoxia. Resulting complications can lead to tissue death, organ dysfunction and even death. Multi-faceted treatment is needed to address the array of complications. SANGUINATE™ (PEGylated, bovine carboxyhemoglobin) has multiple mechanisms of action that may prove effective. It acts both as a carbon monoxidereleasing molecule and as an oxygen transfer agent and is designed to safely perfuse the microvasculature to oxygenate tissue. Designing toxicology studies must not only deal with ensuring the safety of its mechanisms but deal with the potential safety issues of using bovine hemoglobin for both acute and chronic administration. Similar products have previously been shown to have effects on inflammation, vasoactivity, cardiac toxicity and nephrotoxicity as well as pro-coagulant activity. Therefore, studies were designed to thoroughly address the potential of these effects in conjunction with the traditional toxicology and safety pharmacology studies. These toxicology and safety studies were designed to address the FDA’s particular concerns of this novel drug candidate. There were several unique features to this preclinical program including a renal functional study, immunohistochemical and special staining of tissues, measurement of hemoglobin in the urine, measurement of troponin in the serum, inclusion of high dose/high volume groups, and analysis of interference for clinical pathology parameters. To address toxicity and safety concerns of its use as a single or repeating dose therapeutic, SANGUINATE was tested in pivotal studies using three species in repeating doses. There were no adverse effects identified for any doses and therefore, a no observed adverse effect level (NOAEL) was not determined even at dosage levels of 1200 mg/kg (monkey), 1600 mg/kg (pig) and 2400 mg/kg (rat). The completion of these studies permitted SANGUINATE to move into clinical trials.