Pharmacokinetic fate of 14C-labelled fumonisin B1 in swine.

Abstract

The pharmacokinetics of the mycotoxin fumonisn B1 (FB1) were investigated in pigs. Animals were administered 14C-FB1 intravenously (IV; 0.25 microCi, 0.40 mg/kg) or intragastrically (IG; 0.35 microCi, 0.50 mg/kg); separate groups of pigs underwent bile cannulation prior to dosing (groups IV/B and IG/B, respectively). Blood, urine, faeces, (and bile), were collected at specific time intervals over 72 hr, and assayed for specific activity. Following IV dosing, plasma concentration-time profiles were triexponential, with the following mean values: t1/2 alpha, 2.2 min; t1/2 beta, 10.5 min; t1/2 gamma, 182 min; apparent volume distribution (Vd gamma), 2.4 l kg-1; plasma clearance, 9.1 ml min-1 kg-1. After 3 days, clearance of FB1-derived radioactivity from the body had slowed to trace levels; total recoveries in urine and faeces were 21.2% and 58.3%, respectively. In bile-interrupted pigs (IV/B) the absence of the slow terminal elimination phase (gamma) suggested FB1 underwent enterohepatic circulation. Biliary recovery was 70.8% of the IV-dose. Radioactivity remaining in tissues after 72 hr amounted to 19.8% and 11.9% of the dose given to IV and IV/B pigs, respectively; highest activities were measured in liver and kidney equivalent to 1,076 and 486 ng FB1 and/or metabolites per g tissue, respectively. Based on plasma and excretion data, systemic bioavailability following IG dosing was estimated to be a very limited 3-6%. Tissue residue levels following IG dosing were 10-20-fold less than IV dosing.