Toxicokinetic Profiles of Alpha-ketoglutarate Cyanohydrin, a Cyanide Detoxification Product, following Exposure to Potassium Cyanide
Abstract
Poisoning by cyanide can be verified by analysis of the cyanide detoxification product, alpha-ketoglutarate cyanohydrin (alpha-KgCN), which is produced from the reaction of cyanide and endogenous alpha-ketoglutarate. Although alpha-KgCN can potentially be used to verify cyanide exposure, limited toxicokinetic data in cyanide-poisoned animals are available. We, therefore, studied the toxicokinetics of alpha-KgCN and compared its behavior to other cyanide metabolites, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid (ATCA), in the plasma of 31 Yorkshire pigs that received KCN (4 mg/mL) intravenously (IV) (0.17 mg/kg/min). alpha-KgCN concentrations rose rapidly during KCN administration until the onset of apnea, and then decreased over time in all groups with a half-life of 15 min. The maximum concentrations of alpha-KgCN and cyanide were 2.35 and 30.18 microM, respectively, suggesting that only a small fraction of the administered cyanide is converted to alpha-KgCN. Although this is the case, the alpha-KgCN concentration increased >100-fold over endogenous concentrations compared to only a three-fold increase for cyanide and ATCA. The plasma profile of alpha-KgCN was similar to that of cyanide, ATCA, and thiocyanate. The results of this study suggest that the use of alpha-KgCN as a biomarker for cyanide exposure is best suited immediately following exposure for instances of acute, high-dose cyanide poisoning.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 15, 2013
- Accession Number
- ADA615569
Entities
People
- Brendan L. Mitchell
- Brian A Logue
- Gary A. Rockwood
- Gerry R. Boss
- Raj K. Bhandari
- Vikhyat S Bebarta
Organizations
- San Antonio Military Medical Center