Proof Of Concept Efficacy Study Of Intranasal Stabilized Isoamyl Nitrite (Sian) In Rhesus Monkeys Against Acute Cyanide Poisoning

Cyanide is a fast-acting toxicant th inhibits ae obic cellular respiration in mitochondria. Historically, amyl nitrite has been used to treat cyanide poisoning. The objective of this study was to demonstrate the effectiveness of intranasal (IN) administratio of stabili ed isoamyl nitrite (SIAN) against lethal potassium cyanide (KCN) intravenous (IV) challenge in a conscious n nhuman primate (NHP) model. Animals received an IV infusion of a 1 mg/mL KCN solution a a dose of 3.25 mg/kg for 15 min. The IN SIAN treatment was administered at 10 or 12 min post-start of KCN challenge ad monkeys were monitored for survival, clinical signs, respiratory and cardiovascular chang via coninuous telemetry recording. In addition, blood methemoglobin (metHb) levels and blood gases were clo ely monitored after KCN administration. Mid to mid-high doses (13.5 or 27.0 mu L/kg) of SIAN treatme ts at 0 i post KCN challenge significantly increased animal survival. Improvements were also observed in resp atory and cardiovascular functions. The benefits of SIAN treatment decreased when treatment was delayed to 12 min post cyanide exposure. IN administration of SIAN 10 min following initiation of a lethal dose KCN i fusion produced 100% survival (at doses >= 13.5 mu L/kg) in NHP model of lethal cyanide intoxication.