Donald L. Sorby

Increased methotrexate toxicity due to concurrent probenecid administration

Abstract The toxicity of a single dose of methotrexate in the rat was observed to be substantially increased when probenecid was concurrently administered. The increased toxicity was associated with a marked inhibition of the elimination of methotrexate from the blood. The effects of probenecid on the renal and biliary secretion of methotrexate were determined using steady state conditions. Inhibition of biliary secretion accounted for most of the decreased elimination of methotrexate.