Pilot study on the plasma pharmacokinetics of fumonisin B1 in cows following a single dose by oral gavage or intravenous administration.

Abstract

The pharmacokinetic fate of the mycotoxin fumonisin B1 (FB1) was investigated using 4 Holstein cows. Two animals each were administered FB1 intravenously (0.05 or 0.20 mg kg-1) and by oral gavage (1.0 or 5.0 mg kg-1). Blood samples were collected at specific time intervals over 12 hr postdosing, then daily for 13 more days, and analyzed for FB1, the hydroxylated aminopental metabolite, and their conjugates. Following intravenous dosing, the plasma-concentration profile of FB1 underwent a very rapid biexponential decrease, with toxin concentrations falling below detectable levels by 120 min postdosing. No known metabolites were detected in plasma. The similarity in pharmacokinetic parameters between the low- and high-dose animals suggests that FB1 distribution and elimination from blood was not dose-dependent at these levels of toxin administration. Following oral administration of the toxin, no FB1 or known metabolites could be found in the plasma, indicating no or very limited bioavailability in ruminants. The effects of FB1 on plasma-free sphinganine (Sa) and free sphingosine (So) concentrations were also determined. Following oral gavage at either dose, no effects on plasma sphingolipid concentration or Sa/So ratio were noted beyond typical daily variations. At the low intravenous dose (0.05 mg kg-1), changes in Sa or So concentrations were also not apparent. However, following intravenous administration at the higher dose (0.20 mg kg-1), the plasma Sa/So ratio was increased marginally in the one dosed cow, due essentially to a transient increase in Sa concentrations, which rose by approximately 60-65% over average predose levels; So levels remained relatively constant.