Abstract
The pharmacokinetics of D-penicillamine (D-PA) were studied in a patient with Wilson's disease who required regular hemodialysis.
Following a single oral dose of 500mg D-PA on a day without dialysis, the maximum serum concentration was obtained after 4 hours (2.0μg/ml) and D-PA was detected in the serum even after 24 hours (0.9μg/ml). Among the metabolites of D-PA, penicillamine-cystein disulfide (PC) was first found in the serum. Its maximum serum concentration was obtained at 4 hours (31.3μg/ml). PC was still detected in the serum after 24 hours (12.0μg/ml). Penicillamine disulfide (PP) and S-methyl penicillamine (PSMe) were found in the serum 2 and 6 hours following the administration, respectively. These serum levels were higher at 24 hours (3.9, 10.4μg/ml) than at 6 hours.
The same dose of D-PA was administered 2 hours before dialysis to study the results. D-PA and its metabolites were found to be dialyzable. D-PA dialysis clearance was 82.0ml/min, and 10.5% of the administered dose of D-PA was cleared as unchanged during 4 hours of dialysis. Further 57.7% of D-PA including its metabolites was cleared during 4 hours of dialysis. The protein binding capacity of D-PA was thought to be slight on because of its good dialysis clearance.
Based on its chelating ability, a single 500mg dose of D-PA given 2 hours before dialysis appears to be appropriate. Another one or two dialyses without D-PA administration is necessary to eliminate its metabolites.
