r apart from any other drug, food or milk. This permits maximum absorption and reduces the likelihood of inactivation by metal binding in the gastrointestinal tract.
Methodology for determining the bioavailability of penicillamine is not available; however, penicillamine is known to be a very soluble substance.
INDICATIONS - Depen is indicated in the treatment of Wilson’s disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that Depen is not of value in ankylosing spondylitis.
Wilson’s Disease - Wilson’s disease (hepatolenticular degeneration) results from the interaction of an inherited defect and an abnormality in copper metabolism. The metabolic defect, which is the consequence of the autosomal inheritance of one abnormal gene from each parent, manifests itself in a greater positive copper balance than normal. As a result, copper is deposited in several organs and appears eventually to produce pathologic effects most prominently seen in the brain, where degeneration is widespread; in the liver, where fatty infiltration, inflammation, and hepatocellular damage progress to postnecrotic cirrhosis; in the kidney, where tubular and glomerular dysfunction results; and in the eye, where characteristic corneal copper deposits are known as Kayser-Fleischer rings.
Two types of patients require treatment for Wilson’s disease: (1) the symptomatic, and (2) the asymptomatic in whom it can be assumed the disease will develop in the future if the patient is not treated.
Diagnosis, suspected on the basis of family or individual history, physical examination, or a low serum concentration of ceruloplasmin*, is confirmed by the demonstration of Kayser-Fleischer rings or, particularly in the asymptomatic patient, by the quantitative demonstration in a liver biopsy specimen of a concentration of copper in excess of 250 mcg/g dry weight.
Treatment has two objectives:
(1) to minimize dietary intake and absorption of copper.
(2) to promote excretion of copper deposited in tissues.
The first objective is attained by a daily diet that contains no more than one or two milligrams of copper. Such a diet should exclude, most importantly, chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and cereals enriched with copper, and be composed to as great an extent as possible of foods with a low copper content. Distilled or demineralized water should be used if the patient’s drinking water contains more than 0.1 mg of copper per liter.
For the second objective, a copper chelating agent is used.
In symptomatic patients, this treatment usually produces marked neurologic improvement, fading of Kayser-Fleischer rings, and gradual amelioration of hepatic dysfunction and psychic disturbances.
Clinical experience to date suggests that life is prolonged with the above regimen.
Noticeable improvement may not occur for one to three months. Occasionally, neurologic symptoms become worse during initiation of therapy with Depen. Despite this, the drug should not be discontinued permanently. Although temporary interruption may result in clinical improvement of the neurological symptoms, it carries an increased risk of developing a sensitivity reaction upon resumption of therapy (See WARNINGS).
* For quantitative test for serum ceruloplasmin see: M
