Clinical pharmacology of oral intermediate-dose methotrexate with or without probenecid

Serum methotrexate (MTX) levels were measured in 20 patients who received an oral, intermediate-dose MTX regimen preceded by an IV loading dose, with or without probenecid. Plateau serum MTX levels were relatively modest (less than or equal to 2 X 10(-6)M) during the 24 h of treatment. Pretreatment with probenecid (PBC) led to a doubling of the serum MTX level and a significant increase in the area under the concentration-time curve. Nevertheless, oral therapy is not a suitable means of producing sustained, high (10(-5) molar) MTX levels, even with the addition of PBC.