penicillamine-disulfide and penicillamine-cysteine-disulfide

Preliminary studies on the use of high resolution 1H-NMR spectroscopy for the detection of the thiol drug penicillamine and its metabolites in human urine are described. The technique is rapid, simple and requires minimal sample pretreatment. Application of NMR to the qualitative analysis of penicillamine in urine is illustrated by penicillamine disulphide formation from penicillamine following spiking into human urine and the detection of penicillamine, penicillamine disulphide and penicillamine-cysteine disulphide (following oral administration of the drug to patients).

Topics: Cysteine; Humans; Magnetic Resonance Spectroscopy; Penicillamine

D-penicillamine and its major metabolites cysteine-penicillamine disulphide (CP) and penicillamine disulphide (P2) concentrations were measured in plasma from a hemodialysis patient with rheumatoid arthritis. CP and P2 alone were measured in plasma and a plasma ultrafiltrate from a second patient. On penicillamine 250 mg thrice weekly taken after dialysis pre-dialysis penicillamine concentrations were in the range 5.9-9.9 mumol/l. CP and P2 concentrations remained stable (range 139-197 mumol/l and 10-20 mumol/l) over 5 weeks and were of the same order as previously found in patients with normal renal function on higher doses of the drug. On penicillamine 250 mg daily concentrations of metabolites CP and P2 reach 193 mumol/l and 59.2 mumol/l after 2 and 3 weeks respectively. Concentration of metabolites fell by about half and of penicillamine by about a third after dialysis. Concentration of metabolites in ultrafiltrate were on average 75% lower than in plasma. Penicillamine 250 mg thrice weekly given after dialysis appears to be an appropriate dose for hemodialysis patients with rheumatoid arthritis.

Topics: Arthritis, Rheumatoid; Cysteine; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Penicillamine; Renal Dialysis; Time Factors

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

The pharmacokinetic disposition of D-penicillamine and its major metabolites, penicillamine cysteine disulfide ( PSSC ) and penicillamine disulfide ( PSSP ) has been studied in eight patients with rheumatoid arthritis. Plasma concentrations of D-penicillamine, PSSP and PSSC displayed similar characteristics in terms of times to maximum concentrations and biphasic elimination from plasma. Initial t1/2 (alpha) phase ranged from 0.86 to 4.41 h for parent drug and 0.81 to 4.41 h for metabolites. Final t1/2 (beta phase) ranged from 3.4 to 9.45 h for D-penicillamine and 5.62 to 21.7 h for the metabolites. Total drug and metabolites detected in urine accounted for 12.0 to 48.7% of oral drug.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biotransformation; Chromatography, High Pressure Liquid; Cysteine; Dose-Response Relationship, Drug; Female; Humans; Metabolic Clearance Rate; Middle Aged; Penicillamine

Topics: Animals; Chromatography, High Pressure Liquid; Cysteine; Dogs; Humans; Male; Penicillamine; Rats; Rats, Inbred Strains; Time Factors

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