Toxicokinetics and oral bioavailability of fumonisin B1.
The kinetics of fumonisin B1 (FB1) after single doses of 10 mg FB1/kg (po) or 2 mg FB1/kg (i.v.) were studied in male Wistar rats. Serial blood samples were obtained after p.o and i.v. administration. Liver and kidney tissue samples were also obtained after p.o administration. Plasma, liver and kidney concentrations of FB1 were determined by a reversed-phase high-performance liquid chromatographic assay using precolumn 0-phthaldialdehyde derivatisation with fluorescence detection. The FB1 plasma profile could be adequately described by a 2-compartment open model. For FB1, the elimination half-life from plasma was 1.03 h after i.v. and 3.15 h after p.o administration. The apparent volume of distribution and volume of distribution at steady state for FB1 were 0.11 and 0.072 L, respectively, after i.v. administration. The total plasma clearance of FB1 was the same for both the p.o and i.v. routes, 0.072 L/h. After the single p.o dose, FB1 was rapidly absorbed with a Tmax of 1.02 h. The maximum plasma concentration of FB1 was 0.18 microgram/mL. The p.o bioavailability of FB1 was 3.5%. The tissue concentration time data for FB1 fit a 1-compartment open model. Considerable concentrations of FB1 were found in the liver and kidney tissues. The elimination half-lives for FB1 were longer for liver (4.07 h) and kidney (7.07 h) than for plasma (3.15 h). Tissue accumulation of FB1 was evidenced by the tissue/plasma area under the concentration-time curve (AUC) ratios; the AUCtissue/AUCplasma for FB1 was 2.03 in liver and 29.89 in kidney.
Martinez-Larranaga
M R
MR
Department of Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain.
Anadon
A
A
Diaz
M J
MJ
Fernandez-Cruz
M L
ML
Martinez
M A
MA
Frejo
M T
MT
Martinez
M
M
Fernandez
R
R
Anton
R M
RM
Morales
M E
ME
Tafur
M
M
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D037341:Fumonisins; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution
D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1