Zileuton, a 5-lipoxygenase inhibitor in rheumatoid arthritis.
The effects of zileuton, a new 5-lipoxygenase inhibitor, on leukotriene generation and clinical response in rheumatoid arthritis (RA) was studied in a 4-week randomized double blind placebo controlled study at 2 academic rheumatology centers. Zileuton decreased the mean (+/- SEM) ionophore induced synthesis of leukotriene B4 at Week 1 by 70% from 191.2 +/- 28.5 to 57.5 +/- 17.0 ng/ml. A parallel suppression of all major 5-lipoxygenase pathway products was observed. An improvement in clinical variables was observed in the zileuton and placebo treated population. No unique toxicity was identified in this study. Zileuton inhibited 5-lipoxygenase in RA with a suggestion of clinical response with limited toxicity.
Weinblatt
M E
ME
Department of Rheumatology/Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Kremer
J M
JM
Coblyn
J S
JS
Helfgott
S
S
Maier
A L
AL
Petrillo
G
G
Henson
B
B
Rubin
P
P
Sperling
R
R
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; C063449:zileuton; D006918:Hydroxyurea