Because urinary copper excretion can be increased in a variety of liver diseases, penicillamine challenge has been proposed as a means to increase specificity.

A 500 mg dose of penicillamine is given at the beginning and then again at 12 hours during a 24 hour urine collection. Urinary copper excretion greater than 1600 mcg per 24 hours (>25 micromol) is much more likely in Wilsons disease compared with other types of liver disease.

previously in some liteature, colection of 500 mcg cupper in urine after 500 mg was regarded diagnostic for this challenge test.