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Leflunomide ; 새로운 항 류마티스 약제

Other Titles
 Leflunomide; A New Anti-Rheumatic Drug 
Authors
 박용범  ;  이수곤 
Citation
 Journal of the Korean Rheumatism Association (대한류마티스학회지), Vol.7(4) : 323-332, 2000 
Journal Title
 Journal of the Korean Rheumatism Association (대한류마티스학회지) 
ISSN
 1226-8070 
Issue Date
2000
Keywords
Leflunomide ; Disease modifying anti-rheumatic drug ; Rheumatoid arthritis
Abstract
Leflunomide is a novel, isoxazol based disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Its mechanism differs from other DMARDs in that it inhibits de novo pyrimidine synthesis by inhibiting the enzyme dihydroorotate dehydrogenase (DHODH). It is a pro-drug and undergoes rapid conversion to its active form in vivo, A77-1726. A77-1726 inhibits the mitochondrial enzyme DHODH, which plays a key role in the denovo synthesis of pyrimidine ribonucleotide uridine monophosphate (rUMP). Leflunomide prevents clonal expansion of activated lymphocytes by interfering with the cell cycle progression due to inadequate production of rUMP and utilizing mechanisms involving p53. The relative lack of toxicity of A77-1726 on nonlymphoid cells may be due to the ability of these cells to fulfill their ribonucleotide requirements by use of salvage pyrimidine pathway, which makes them less dependent on de novo synthesis . Several phase II clinical trials of patients with RA revealed that leflunomide was effective and well tolerated. Large-scale phase III clinical trials have shown that leflunomide (20mg/day) provided a statistically significant clinical benefit and prevention of radiographic progression in comparison to placebo. The clinical benefits of leflunomide were similar to or greater than methotrexate and sulfasalazine. Now, many multi-national studies are in progress and planning, including combination therapy with other DMARD. In future, those studies will provide us more information about the effectiveness and potential adverse effect of leflunomide.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Yong Beom(박용범)
Lee, Soo Kon(이수곤)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171714
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