D-Penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3.

Abstract

Sulphoxidation of carbocysteine, a drug structurally similar to D-penicillamine, displays a skewed distribution within a population. In 66 patients with rheumatoid arthritis (RA) a significant association between impaired sulphoxidation and toxicity (p less than 0.001) was found; HLA-DR3, although associated with toxicity (p less than 0.05), appeared to be an independent risk factor of most importance in the group with extensive sulphoxidation. The relative risk of toxicity in a patient possessing either DR3 or impaired sulphoxidation was 25. The prevalence of poor sulphoxidizers within this group of RA patients was increased compared to that in a previous population study and requires further investigation. Our findings explain a number of the toxic phenomena associated with D-penicillamine administration in RA.

• Authors: P Emery, G S Panayi, G Huston, K I Welsh, S C Mitchell, R R Shah, J R Idle, R L Smith, R H Waring
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 11 Issue 5 Pg. 626-32 (Oct 1984) ISSN: 0315-162X [Print] Canada
• PMID: 6334741 (Publication Type: Journal Article)

Chemical References

• HLA-DR3 Antigen
• HLA-DR4 Antigen
• Histocompatibility Antigens Class II
• Carbocysteine
• Penicillamine
• Cysteine

Topics

• Adult
• Aged
• Arthritis, Rheumatoid (drug therapy, genetics, metabolism)
• Biotransformation
• Carbocysteine (metabolism)
• Cysteine (analogs & derivatives)
• Female
• HLA-DR3 Antigen
• HLA-DR4 Antigen
• Histocompatibility Antigens Class II (genetics)
• Humans
• Male
• Middle Aged
• Penicillamine (adverse effects, metabolism, therapeutic use)
• Risk