title: The Vitamin B12Analog Cobinamide Is an Effective Antidote for Oral Cyanide Poisoning.
abstract: Cyanide is a major chemical threat, and cyanide ingestion carries a higher risk for a supra-lethal dose exposure compared to inhalation but provides an opportunity for effective treatment due to a longer treatment window and a gastrointestinal cyanide reservoir that could be neutralized prior to systemic absorption. We hypothesized that orally administered cobinamide may function as a high-binding affinity scavenger and that gastric alkalinization would reduce cyanide absorption and concurrently increase cobinamide binding, further enhancing antidote effectiveness.
  
  
  
  Thirty New Zealand white rabbits were divided into five groups and were given a lethal dose of oral cyanide poisoning (50 mg). The survival time of animals was monitored with oral cyanide alone, oral cyanide with gastric alkalinization with oral sodium bicarbonate buffer (500 mg), and in combination with either aquohydroxocobinamide or dinitrocobinamide (250 mM). Red blood cell cyanide concentration, plasma cobinamide, and thiocyanate concentrations were measured from blood samples.
  
  
  
  In cyanide ingested animals, oral sodium bicarbonate alone significantly prolonged survival time to 20.3 ± 8.6 min compared to 10.5 ± 4.3 min in saline-treated controls, but did not lead to overall survival. Aquohydroxocobinamide and dinitrocobinamide increased survival time to 64 ± 41 (p < 0.05) and 75 ± 16.4 min (p < 0.001), respectively. Compared to aquohydroxocobinamide, dinitrocobinamide showed greater systemic absorption and reduced blood pressure. Dinitrocobinamide also markedly increased the red blood cell cyanide concentration. Under all conditions, the plasma thiocyanate concentration gradually increased with time.
  
  
  
  This study demonstrates a promising new approach to treat high-dose cyanide ingestion, with gastric alkalinization alone and in combination with oral cobinamide for treating a supra-lethal dose of orally administered cyanide in rabbits.
authors.affiliation: Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA. jangwl@uci.edu.
authors.forename: Jangwoen
authors.initials: J
authors.lastname: Lee
authors.affiliation: Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA.
authors.forename: Sari B
authors.initials: SB
authors.lastname: Mahon
authors.affiliation: Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mukai
authors.affiliation: Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Burney
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA, 92093-0652, USA.
authors.forename: Behdod S
authors.initials: BS
authors.lastname: Katebian
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA, 92093-0652, USA.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
authors.forename: Vikhyat S
authors.initials: VS
authors.lastname: Bebarta
authors.affiliation: Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA.
authors.forename: David
authors.initials: D
authors.lastname: Yoon
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA, 92093-0652, USA.
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Boss
authors.affiliation: Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA.|Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, 92868, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brenner
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000863:Antacids / Q000627:therapeutic use*; D000931:Antidotes / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003038:Cobamides / Q000097:blood / Q000627:therapeutic use*; D003486:Cyanides / Q000037:antagonists & inhibitors* / Q000506:poisoning*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008297:Male; D011817:Rabbits; D017693:Sodium Bicarbonate / Q000627:therapeutic use; D013057:Spectrum Analysis; D015996:Survival Rate; D013861:Thiocyanates / Q000097:blood; D013997:Time Factors
chemical_list: D000863:Antacids; D000931:Antidotes; D003038:Cobamides; D003486:Cyanides; D013861:Thiocyanates; C017142:cobinamide; D017693:Sodium Bicarbonate; C031760:thiocyanate
keywords: Cobinamide; Diffuse optical spectroscopy; Gastric alkalinization; Oral cyanide poisoning