The hepatic uptake and biliary excretion of the neuroprotective drug 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(f)-quinoxaline (NBQX) was studied in rat liver. In the isolated single-pass perfused rat liver preparation NBQX was infused in protein-free Krebs-Henseleit bicarbonate buffer at input concentrations ranging from 0.5 to 15 microM. The hepatic uptake could be characterized as a pseudo first-order unidirectional process with an apparent half-life of 5.8 min. Significantly higher concentrations of NBQX were measured in bile compared to perfusate with a maximal ratio at the lowest input concentration (approx. 2400-fold). Hepatic uptake and biliary excretion of NBQX exhibited saturation at increasing input concentrations, indicating an active transport mechanism. The uptake process could be described by Michaelis-Menten kinetics resulting in a Km,uptake of 2.2 microM. The corresponding maximal uptake rate (Vmax,uptake) was calculated to be 103 nmol/min. The maximal biliary excretion rate was estimated to be 58 nmol/min. The rate-limiting factor in the overall hepatic elimination was thus biliary excretion. Co-infusion with the uricosuric drug probenecid resulted in significantly decreased hepatic uptake and biliary excretion. These data suggest that NBQX is eliminated by an organic anion transport system in rat liver which is sensitive to probenecid.