Methotrexate pharmacokinetics.

A pharmacokinetic model is presented to predict the detailed distribution and excretion of methotrexate in several mammalian species over a wide range of doses. Anatomical compartments include liver, kidneys, gastrointestinal tract, muscle, and plasma; multicompartment representations simulate biliary excretion and movement of drug through the gastrointestinal tract with partial reabsorption. Tissue‐to‐plasma distribution coefficients include linear and strong saturable (presumed dihydrofolate reductase) effects. Required parameters are measured directly or estimated on the basis of physiological principles for mice, rats, dogs, and man.