Pharmacology and pharmacokinetics of methotrexate in rheumatic disease. Practical issues in treatment and design.

Methotrexate (MTX) is among the most effective drugs for treatment of rheumatoid arthritis (RA) and has proven valuable in the treatment of multiple other disorders of immune regulation. Methotrexate has been administered at a wide range of doses and dose intervals, in conjunction with multiple other drugs, and in patients with a broad range of concomitant disorders. To design a safe and effective MTX treatment plan for an individual patient, the provider must have knowledge of the pharmacology and drug interactions of this effective but potentially dangerous medication. The first section of this article reviews MTX structure, pharmacology, pharmacokinetics, and mechanisms of action in rheumatic disease. The following section examines factors that can be used to increase MTX efficacy and decrease toxicity. The relevant clinical pharmacology is organized in terms of absorption, distribution, metabolism, and elimination.