Alteration of active transport.

1. Penicillins-probenecid

- probenecid approved to play a role in the tubular by blocking the secretion of
penicillin then enhance the concentration, effectiveness by the factor of 2-fold
to 4-fold elevation of serum also it decreases renal excretion of methotrexate.

2. Methotrexate-NSAIDs

- NSAIDs increase the activity and toxicity of methotrexate also toxicity to
ketoprofen.