Serum Folate: A Pharmacodynamic Biomarker of Intracellular Nitrosylcobalamin Activity Following Intravenous Administration in Dogs

Serum Folate: A Pharmacodynamic Biomarker of Intracellular Nitrosylcobalamin Activity Following Intravenous Administration in Dogs

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

Anticancer Research

2012

2012-10

Background/Aim: Cobalamin and folate are interdependent co-factors of the methionine synthase pathway. This study evaluated the effect of intravenously-administered nitrosylcobalamin (NO-Cbl), a vitamin B12 analog, on serum folate concentrations in healthy dogs. Materials and Methods: Four dogs received a 10-mg/kg, 20-mg/kg and 40-mg/kg intravenous bolus dose of NO-Cbl, with a 14-day washout period between doses. Blood samples were collected at baseline and post-dosing, and serum cobalamin and folate concentrations were measured. Results: For each dose, serum cobalamin concentrations were inversely correlated with serum folate concentrations. Spearman rank correlation coefficient values were -0.976 (10 mg/kg, p<0.0096), and -1.0 (20 mg/kg, p<0.008; 40 mg/kg, p<0.0046). Conclusion: Cellular uptake of NO-Cbl, following intravenous administration exerted a biological effect on folate similar to that previously described for other vitamin B12 analogs. Serum folate concentration may serve as a pharmacodynamic biomarker of intracellular nitrosylcobalamin activity following intravenous administration.

apo2l/trail; biomarker; cells; cobalamin; disease; dogs; Folate; homocysteine; methylmalonic acid; nitric-oxide; Nitrosylcobalamin; Oncology; pharmacokinetics; supplementation; suppression; vitamin B-12; vitamin B-12

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Journal Article

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4307-4312

10

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