Methotrexate. I. Pharmacology and pharmacokinetics

Chemical, physical, and metabolic processes of methotrexate are reviewed. The effects of the drug on intracellular metabolic processes, due to the inhibitory action of methotrexate on the enzyme dihydrofolate reductase, show that the result of this inhibition is more complex and is not limited to blockade of the reduction of folic acid alone. Although rescue methods are important in prevention of lethal effects of methotrexate, some metabolic pathways are insufficiently rescued, resulting in toxic reactions following methotrexate administration. Efficient use of pharmacokinetic models may help in reducing these unwanted actions of methotrexate in cancer chemotherapy.