D-Penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3.
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.
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation; D002233:Carbocysteine / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives*; D005260:Female; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D012306:Risk
D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D002233:Carbocysteine; D010396:Penicillamine; D003545:Cysteine