Appropriate administration schedule of D-penicillamine for pediatric Wilson's disease patients based on urinary copper excretion

The purpose of this study was to increase the amount of copper excreted resulting from the administration of D-penicillamine (DP) in pediatric Wilson's disease (WD) patients. By measuring the urinary copper excretion after adjusting the administration schedules, the appropriate timing for DP administration was investigated. The subjects were three brothers with pediatric WD. The initial daily dose of DP was 5 mg/kg/day, and gradually increased to the maintenance dose of 20 mg/kg/day. Until the maintenance daily dose was reached, DP was administered 2 h after the morning and evening meal. After reaching the maintenance daily dose of DP, the appropriate timing for taking DP was investigated in both the morning and evening. Three schedules of DP administration were compared: 2 h after meals; 30 min before meals (with fasting); and 1 h before the morning and 1.5 before the evening meal (direction 1). The resulting urinary copper excretion on each dosing schedule was compared. Little difference was found in urinary copper excretion on the first two schedules, i.e., 2 h after meals and 30 min before meals. When DP was administered 30 min before meals, urinary copper excretion [mug/day] was 1173 in the first brother, 918 in the second, and 875 in the third. When DP was administered according to direction 1, however, urinary copper excretion was increased significantly to 1701 in the first brother, 2701 in the second, and 3808 in the third. It is known that the efficiency of urinary copper excretion with DP administration depends on the maintenance of chelating ability after absorption from the gastrointestinal tract. Our results indicate that the excretion was lower when DP was administered 2 h after or 30 min before meals (with fasting), as recommended in the package insert. Thus to achieve better copper excretion efficiency, direction 1 is recommended for WD patients.