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.

Fumonisin Toxicosis in Swine: An Overview of Porcine Pulmonary Edema and Current Perspectives

“…In rats, fumonisins are absorbed poorly and excreted rapidly (apparently as parent compound) by the liver and to a much lesser degree through the kidney (23)(24)(25)(26). The pharmacokinetics of liver >> kidney > large intestine > brain > lung, heart, adrenal gland, spleen (27,28). In swine, plasma radioactivity declined in a triexponential manner following intravenous administration of [ 14 C]FB 1 with a large volume of distribution (2.4 L/kg) and moderately rapid plasma clearance (9.1 mL/min/kg) (27).…”

“…The pharmacokinetics of liver >> kidney > large intestine > brain > lung, heart, adrenal gland, spleen (27,28). In swine, plasma radioactivity declined in a triexponential manner following intravenous administration of [ 14 C]FB 1 with a large volume of distribution (2.4 L/kg) and moderately rapid plasma clearance (9.1 mL/min/kg) (27). Only trace levels of radioactivity remained in plasma after 3 days.…”

“…When FB 1 was given intragastrically, bioavailability was 3-6%. After 3 days, the total remaining tissue residues were 10-to 20-fold lower than after the intravenous dose (27). Fumonisin residues accumulated in liver and kidney when pigs were fed [ 14 C]FB 1 at dietary concentrations of 2-3 ppm for 24 days (28).…”

Possible Role of Phosphatidylcholine and Sphingomyelin on Fumonisin B1-mediated Toxicity

“…), the plasma disappearance rate was calculated 10.5 min in pigs 33) . Total 21.2% and 58.3% of the radioactivity are recovered in urine and feces for three days, respectively.…”

Avaliação de biomarcadores da exposição humana à fumonisina B1 nos alimentos em municípios dos estados de São Paulo e Santa Catarina, Brasil

“…Estudos avaliando a toxicocinética da FB 1 foram conduzidos em macacos-vervet (SHEPHARD et al, 1994), suínos (PRELUSKY; TRENHOLM; SAVARD, 1994;DILKIN et al, 2003) e bovinos (SORIANO et al, 2005) e demonstram que a toxina é pouco absorvida quando administrada por via oral, rapidamente encontrada na circulação, excretadas em pequenas quantidades na urina e recuperada em sua estrutura original através das fezes (WHO, 2000). A FB 1 é acumulada em pequenas quantidades em fígado e rins e pode também ser excretada na bile apesar da baixa absorção, podendo ocorrer algumas recirculações entero hepáticas (ORSI et al, 2009).…”