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


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).


CONCLUSIONS
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.
BNOAT Oncology, Inc, Akron Innovation Campus, 411 Wolf Ledges Parkway, Suite 105, Akron, OH 44311, USA.
Annette M
AM
Sysel
Walter I
WI
Horne
Jörg M
JM
Steiner
Jan S
JS
Suchodolski
Joseph A
JA
Bauer
D061605:Administration, Intravenous; D000818:Animals; D054316:Biomarkers, Pharmacological / Q000097:blood*; D004285:Dogs; D005492:Folic Acid / Q000097:blood*; D008297:Male; D009603:Nitroso Compounds / Q000008:administration & dosage* / Q000097:blood; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
D054316:Biomarkers, Pharmacological; D009603:Nitroso Compounds; C113298:nitrosylcobalamin; D005492:Folic Acid; D014805:Vitamin B 12