Studies on the metabolism of D-penicillamine and its interaction with probenecid in cystinuria and rheumatoid arthritis.
Four patients with recurrent cystine stones and 5 with rheumatoid arthritis (RA) were studied. After a single dose of D-penicillamine to cystinuric patients, cystine excretion decreased considerably. Cysteine-penicillamine mixed disulfide (CSSP) and penicillamine disulfide (PSSP) metabolites appeared within 1-2 h (CSSP/PSSP approximately equal to 4.8-8.6). In RA, cystine excretion remained negligible (CSSP/PSSP approximately equal to 1.4-2.9). With daily D-penicillamine in RA (CSSP/PSSP ratios were usually greater than 7 in those with favorable clinical response. CSSP/PSSP ratios may help to predict prognosis and adjust penicillamine dosage. Coadministration of probenecid is contraindicated in hyperuricemic cystinuric patients because of increased cystine and decreased CSSP and PSSP excretion.
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D003545:Cysteine / Q000031:analogs & derivatives / Q000652:urine; D003555:Cystinuria / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000652:urine; D010865:Pilot Projects; D011339:Probenecid / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
C036069:penicillamine disulfide; C030163:penicillamine cysteine disulfide; D010396:Penicillamine; D003545:Cysteine; D011339:Probenecid