The relationship of sulfoxidation status to efficacy and toxicity of penicillamine in the treatment of rheumatoid arthritis

✍ Scribed by R. Madhok; A. Zoma; H. I. Torley; H. A. Capell; R. Waring; J. A. Hunter

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 328 KB
• Volume: 33
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.1780330416

✦ Synopsis

Penicillamine shows some structural similarities to carbocysteine. The ability to oxidize carbocysteine, i.e., the sulfoxidation status, shows a bimodal distribution in the general population. In this study, sulfoxidation status was determined in 50 of 60 rheumatoid arthritis patients receiving penicillamine. We found that poor sulfoxidation status, compared with good sulfoxidation status, was associated with a 3.9 times higher incidence of toxicity.

Second-line agents such as penicillamine and gold sodium thiomalate play an important role in the management of rheumatoid arthritis (RA). However, toxic reactions are frequent, limiting the potential benefit of the drugs. Monitoring of these treatments is expensive and time-consuming. D-penicillamine (DP) shows structural similarities to the mucolytic agent carbocysteine (Scarboxymethylcysteine). One of us (RW) has previously shown that there is wide variation in the capacity of individuals to oxidize carbocysteine to sulfoxide metabolites, which is largely genetically determined (1,2). Pharrnacokinetic studies of S-labeled DP show that 4% of the ingested dose is excreted in the urine as -From the