Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.
OBJECTIVE
To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism.


METHODS
Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment.


RESULTS
Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24.


CONCLUSIONS
The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.
Addyman
R
R
Clinical Pharmacology Unit (Rheumatism Research), Chapel Allerton Hospital, Leeds, United Kingdom.
Beyeler
C
C
Astbury
C
C
Bird
H A
HA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000652:urine; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D005937:Glucaric Acid / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000652:urine
D018501:Antirheumatic Agents; D015415:Biomarkers; D003404:Creatinine; D005937:Glucaric Acid