Pharmacokinetics of next generation cyanide antidote sulfanegen in rabbits

Abstract

Aim: Sulfanegen has been shown to be an effective next generation cyanide antidote in multiple animal studies. Sulfanegen detoxifies cyanide by acting as a sulfur donor, converting cyanide to thiocyanate through the enzyme 3-mercaptopyruvate (3-MP) sulfurtransferase. The current study was performed to determine the PK behavior of sulfanegen in rabbits and compare it to current US FDA-approved cyanide therapeutics. Methods: Plasma sulfanegen concentrations, as 3-MP (i.e., sulfanegen is a prodrug that converts to the active sulfur donor, 3-MP, upon administration), were monitored using LC–MS/MS following intramuscular administration of sulfanegen in rabbits. Results: Concentrations of 3-MP rapidly increased following sulfanegen administration, indicating rapid absorption and distribution of 3-MP throughout the body. Elimination of 3-MP was also relatively rapid; the calculated half-life was approximately 114 min. A one-compartment model with first-order distribution and elimination was used to describe the PK behavior of 3-MP. Conclusion: Overall, the PK characteristics of sulfanegen were found to be well suited for the rapid treatment of cyanide poisoning.