Pharmacokinetics of intravenous nitrosylcobalamin, an antitumor agent, in healthy Beagle dogs: a pilot study.

Abstract

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 × 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.

CONCLUSION:

These results can be used to determine the dose and dosing intervals for clinical trials evaluating NO-Cbl in humans and companion animals.

• Authors: Annette M Sysel, Walter I Horne, Jörg M Steiner, Jan S Suchodolski, Joseph A Bauer
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 9 Pg. 3749-52 (Sep 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22993315 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Nitroso Compounds
• nitrosylcobalamin
• Vitamin B 12

Topics

• Animals
• Antineoplastic Agents (administration & dosage, blood, pharmacokinetics)
• Dogs
• Injections, Intravenous
• Male
• Nitroso Compounds (administration & dosage, blood, pharmacokinetics)
• Pilot Projects
• Vitamin B 12 (administration & dosage, analogs & derivatives, blood, pharmacokinetics)