title: Pharmacokinetics of intravenous nitrosylcobalamin, an antitumor agent, in healthy Beagle dogs: a pilot study.
abstract: OBJECTIVE
  Nitrosylcobalamin (NO-Cbl) is a cobalamin-based anti-tumor agent. This study evaluated the pharmacokinetic parameters of NO-Cbl following intravenous administration in dogs.
  
  
  METHODS
  Four dogs received 10 mg/kg, 20 mg/kg and 40 mg/kg intravenous bolus doses of NO-Cbl, with a 14-day washout period between doses. Blood samples were collected at baseline and post-dosing, and noncompartmental pharmacokinetic parameters were determined.
  
  
  RESULTS
  Average peak serum concentrations of 2265, 5523 and 13,866 pg/mL were achieved following single-dose bolus intravenous administration of 10 mg/kg, 20 mg/kg and 40 mg/kg of NO-Cbl respectively. The average area under the curve was 12,697 h × pg/mL, 24,497 h × pg/mL and 44,976 h × pg/mL respectively, with an average elimination half-life of 16.2 h, 13.5 h and 13.1 h respectively.
  
  
  CONCLUSIONS
  These results can be used to determine the dose and dosing intervals for clinical trials evaluating NO-Cbl in humans and companion animals.
authors.affiliation: BNOAT Oncology, Inc, Akron Innovation Campus, Akron, OH, USA.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Sysel
authors.forename: Walter I
authors.initials: WI
authors.lastname: Horne
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Steiner
authors.forename: Jan S
authors.initials: JS
authors.lastname: Suchodolski
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Bauer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D007275:Injections, Intravenous; D008297:Male; D009603:Nitroso Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010865:Pilot Projects; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D009603:Nitroso Compounds; C113298:nitrosylcobalamin; D014805:Vitamin B 12