Abstract
Leflunomide is a new disease-modifying anti-rheumatic drug (DMARD) that is classified as an isoxazol, and is rapidly converted from its prodrug form to its active metabolite, A77 1726, by first-pass metabolism in the gut and liver. At therapeutic doses (20 mg/d) in rheumatoid arthritis (RA) patients, A77 1726 blocks the de novo synthesis of pyrimidines by inhibiting dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in pyrimidine production (1–4) necessary for the clonal expansion of activated T and B lymphocytes. The following overview will address the mode of action and the preclinical and clinical experience with leflunomide in the treatment of RA.
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Emery, P., Scott, D.L., Strand, V. (2002). Leflunomide. In: Tsokos, G.C. (eds) Modern Therapeutics in Rheumatic Diseases. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-239-5_8
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