Studies with 35S-labelled DL-Penicillamine in Patients with Wilson's Disease

Abstract

The fate of orally administered ³⁵S DL-penicillamine has been studied in six patients with Wilson's disease. Penicillamine is rapidly absorbed from the gut reaching a concentration of between 2 and 5 per cent of the dose per litre of plasma at one or two hours after ingestion. Thereafter the concentration falls rapidly but the label can still be detected in the plasma up to 48 hours. Penicillamine becomes bound to serum albumin so that, by 24 hours, only 20 per cent of the label is able to pass through a semi-permeable membrane. For several hours after administration penicillamine is cleared from the plasma at a rate approximating to creatinine clearance. After protein binding has occurred the rate of excretion of the amino acid falls off so that very little appears in the urine after 24 hours. Autoradiographic studies showed that penicillamine could be detected in plasma mostly as penicillamine. In urine, where detection is easier, it was found not only as penicillamine but also as penicillamine-cysteine disulphide. A number of minor components, all capable of being oxidized to penicillamine sulphonic acid, were also present. Two patients who had had toxic reactions to penicillamine did not appear to handle the drug differently from the other four.