Abstract
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. CONCLUSION: 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.
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Selected References
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- Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
- Beck F. J., Whitehouse M. W. Effect of adjuvant disease in rats on cyclophosphamide and isophosphamide metabolism. Biochem Pharmacol. 1973 Oct 1;22(19):2453–2468. doi: 10.1016/0006-2952(73)90348-1. [DOI] [PubMed] [Google Scholar]
- Cawthorne M. A., Palmer E. D., Green J. Adjuvant-induced arthritis and drug-metabolizing enzymes. Biochem Pharmacol. 1976 Dec 15;25(24):2683–2688. doi: 10.1016/0006-2952(76)90257-4. [DOI] [PubMed] [Google Scholar]
- Hunter J., Maxwell J. D., Carrella M., Stewart D. A., Williams R. Urinary D-glucaric-acid excretion as a test for hepatic enzyme induction in man. Lancet. 1971 Mar 20;1(7699):572–575. doi: 10.1016/s0140-6736(71)91166-4. [DOI] [PubMed] [Google Scholar]
- Hunter J., Maxwell J. D., Stewart D. A., Williams R. Urinary D-glucaric acid excretion and total liver content of cytochrome P-450 in guinea-pigs: relationship during enzyme induction and following inhibition of protein synthesis. Biochem Pharmacol. 1973 Mar 15;22(6):743–747. doi: 10.1016/0006-2952(73)90405-x. [DOI] [PubMed] [Google Scholar]
- Lecamwasam D. S., Franklin C., Turner P. Effect of phenobarbitone on hepatic drug-metabolizing enzymes and urinary D-glucaric acid excretion in man. Br J Clin Pharmacol. 1975 Jun;2(3):257–262. doi: 10.1111/j.1365-2125.1975.tb01584.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MARSH C. A., CARR A. J. CHANGES IN ENZYME ACTIVITY, RELATED TO D-GLUCARIC ACID SYNTHESIS, WITH AGE, PREGNANCY AND MALIGNANCY. Clin Sci. 1965 Apr;28:209–217. [PubMed] [Google Scholar]
- Morton D. M., Chatfield D. H. The effects of adjuvant-induced arthritis on the liver metabolism of drugs in rats. Biochem Pharmacol. 1970 Feb;19(2):473–481. doi: 10.1016/0006-2952(70)90202-9. [DOI] [PubMed] [Google Scholar]
- Mowat A. P. Developmental effects on liver D-glucuronolactone dehydrogenase levels and on D-glucaric acid excretion in urine; hormonal effects on D-glucaric acid excretion in urine. J Endocrinol. 1968 Dec;42(4):585–590. doi: 10.1677/joe.0.0420585. [DOI] [PubMed] [Google Scholar]
- Park B. K., Breckenridge A. M. Clinical implications of enzyme induction and enzyme inhibition. Clin Pharmacokinet. 1981 Jan-Feb;6(1):1–24. doi: 10.2165/00003088-198106010-00001. [DOI] [PubMed] [Google Scholar]
- Simmons C. J., Davis M., Dordoni B., Williams R. Urinary D-glucaric acid assay by an improved enzymatic procedure. Clin Chim Acta. 1974 Feb 28;51(1):47–51. doi: 10.1016/0009-8981(74)90060-6. [DOI] [PubMed] [Google Scholar]
- Sotaniemi E. A., Medzihradsky F., Eliasson G. Glucaric acid as an indicator of use of enzyme-inducing drugs. Clin Pharmacol Ther. 1974 Apr;15(4):417–423. doi: 10.1002/cpt1974154417. [DOI] [PubMed] [Google Scholar]
- van der Linden S., Valkenburg H. A., Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984 Apr;27(4):361–368. doi: 10.1002/art.1780270401. [DOI] [PubMed] [Google Scholar]
