Serum folate: a pharmacodynamic biomarker of intracellular nitrosylcobalamin activity following intravenous administration in dogs.

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 co-efficient 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.