penicillamine-disulfide and Cystinuria

Topics: Cystinuria; Humans; Penicillamine; Pipecolic Acids

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.

Topics: Arthritis, Rheumatoid; Cysteine; Cystinuria; Drug Therapy, Combination; Female; Humans; Male; Penicillamine; Pilot Projects; Probenecid; Time Factors

Penicillamine disulfides have been analysed by automatic amino acid analysis. Because the free thiol reacts poorly with ninhydrin, other detection methods are preferred, particularly high pressure liquid chromatography using an electrochemical detector or gas chromatography with a flame ionization detector. Pharmacokinetic studies have now been reported using these techniques. With patients on established penicillamine regimes, the concentration of free penicillamine in the plasma has been found to vary between 4 and 20 microM depending on dosage and time of administration. Disulfide concentration is higher than this by a factor of 3 or 4 and an even greater quantity is attached to plasma and tissue proteins.

Topics: Arthritis, Rheumatoid; Chromatography, Gas; Chromatography, High Pressure Liquid; Cystinuria; Dose-Response Relationship, Drug; Hepatolenticular Degeneration; Humans; Penicillamine; Protein Binding

Administration of penicillamine reduced the concentration of cystine in the plasma and urine of patients with cystinuria; renal clearance of cystine, lysine, and arginine remained unchanged. Cysteine-penicillamine disulfide and penicillamine disulfide were detected in the plasma.

Topics: Arginine; Blood; Cysteine; Cystine; Cystinuria; Drug Therapy; Humans; Lysine; Penicillamine; Sulfides; Urine