Pharmacokinetics of Intravenous Nitrosylcobalamin, an Antitumor Agent, in Healthy Beagle Dogs: A Pilot Study

Pharmacokinetics of Intravenous Nitrosylcobalamin, an Antitumor Agent, in Healthy Beagle Dogs: A Pilot Study

Sysel A M; Horne W I; Steiner J M; Suchodolski J S; Bauer J A

Anticancer Research

2012

2012-09

Background/Aim: Nitrosylcobalamin (NO-Cbl) is a cobalamin-based anti-tumor agent. This study evaluated the pharmacokinetic parameters of NO-Cbl following intravenous administration in dogs. Materials and 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 x pg/mL, 24,497 h x pg/mL and 44,976 h x pg/mL respectively, with an average elimination half-life of 16.2 h, 13.5 h and 13.1 h respectively. Conclusion: These results can be used to determine the dose and dosing intervals for clinical trials evaluating NO-Cbl in humans and companion animals.

apo2l/trail; canine organs; cobalamin; cobalamin vitamin-b-12; dogs; intravenous; nitric-oxide; Nitrosylcobalamin; Oncology; pharmacokinetics; protein; release; suppression; transcobalamin-ii; transport; vitamin B-12

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Journal Article

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3749-3752

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