This study was conducted to characterize the disposition, oral bioavailability, and tissue distribution of zearalenone in rats. The pharmacokinetics and tissue distribution of zearalenone were studied after intravenous (i.v.) or oral (p.o.) administration at doses ranging from 1 to 8 mg/kg in intact and bile duct-cannulated rats. Serum, bile, and urine concentrations were determined by liquid chromatography and mass spectroscopy (LC/MS/MS) and tissue concentrations by high-performance liquid chromatography (HPLC)/fluorescence detection assays. Noncompartmental methods were used for pharmacokinetic analysis. Average Cl(s) (range 5.0-6.6 L/h/kg) and V(dss) (range 2-4.7 L/kg) remained unaltered over an i.v. dose range from 1 to 8 mg/kg, and area under the concentration-time curve (AUC) and initial peak concentrations increased linearly with dose. Minimal quantities of zearalenone were excreted unchanged in urine (f(e,urine) 0.5 +/- 0.2%) and bile (f(e,bile) 0.91 +/- 0.64%). After p.o. administration of 8 mg/kg, zearalenone was rapidly absorbed and serum concentration-time profiles showed a distinct second peak. The absolute oral bioavailability was low (2.7%). Comparing bile duct-cannulated to intact rats at a dose of 8 mg/kg, the impact of biliary excretion on overall pharmacokinetics was more pronounced after p.o. than after i.v. administration. Upon i.v. infusion to steady state, the highest zearalenone concentration was found in small intestine, followed by kidneys, liver, adipose tissue, and lung. Zearalenone concentrations in stomach, heart, brain, spleen, muscle, and testes were lower than those found in serum. The pharmacokinetics and tissue distribution data from this study may be useful to develop physiologically based pharmacokinetic (PBPK) models for zearalenone and subsequently to predict the pharmacokinetics and toxicity in humans.