Leflunomide for the treatment of rheumatoid arthritis

被引:45
作者
Miceli-Richard, C [1 ]
Dougados, M [1 ]
机构
[1] Univ Paris 05, AP HP, Cochin Hosp, Paris, France
关键词
dihydro-orotate dehydrogenase; DMARDs; leflunomide; rheumatoid arthritis;
D O I
10.1517/14656566.4.6.987
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
Leflunomide (Arav(R), Aventis Pharmaceuticals) is an immunomodulating drug that interferes with the metabolism of pyrimidine by inhibiting dihydroorotate dehydrogenase (DHO-DH) in mitochondria, thereby blocking T- and B cell proliferation. Antibody production is also affected by DHO-DH blockade. Other immunomodulatory effects of leflunomide have also been reported. Symptomatic and structural effects of leflunomide in active rheumatoid arthritis have been strictly evaluated by double-blind, randomised, placebo-controlled studies that were aimed at validating its use in rheumatoid arthritis. Further trials are now required to confirm efficacy and safety of this drug in combination with other agents.
引用
收藏
页码:987 / 997
页数:11
相关论文
共 31 条
[1]
Bartlett RR, 1996, TRANSPLANT P, V28, P3074
[2]
BRAULT I, 2002, ARTHRITIS RHEUM, V46
[3]
Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: Tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide [J].
Brazelton, TR ;
Morris, RE .
CURRENT OPINION IN IMMUNOLOGY, 1996, 8 (05) :710-720
[4]
Leflunomide: mode of action in the treatment of rheumatoid arthritis [J].
Breedveld, FC ;
Dayer, JM .
ANNALS OF THE RHEUMATIC DISEASES, 2000, 59 (11) :841-849
[5]
Cao WW, 1996, TRANSPL P, V28, P3079
[6]
CHERWINSKI HM, 1995, J PHARMACOL EXP THER, V275, P1043
[7]
LEFLUNOMIDE INTERFERES WITH PYRIMIDINE NUCLEOTIDE BIOSYNTHESIS [J].
CHERWINSKI, HM ;
BYARS, N ;
BALLARON, SJ ;
NAKANO, GM ;
YOUNG, JM ;
RANSOM, JT .
INFLAMMATION RESEARCH, 1995, 44 (08) :317-322
[8]
CHERWINSKI HM, 1995, J PHARMACOL EXP THER, V272, P460
[9]
The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase [J].
Davis, JP ;
Cain, GA ;
Pitts, WJ ;
Magolda, RL ;
Copeland, RA .
BIOCHEMISTRY, 1996, 35 (04) :1270-1273
[10]
DOUGADOS M, 2002, ANN RHEUM DIS S1, V61