Serum copper concentration and hepatic enzyme induction during long-term therapy with anticonvulsants

We evaluated hepatic enzyme induction by measuring urinary D-glucaric acid and serum gamma-glutamyltransferase in a group of 40 adult epileptics of both sexes who were receiving long-term treatment with phenobarbital and (or) phenytoin. Total concentrations of copper and ceruloplasmin in their serum and the oxidase activity of ceruloplasmin were significantly greater than in the control group. However, non-ceruloplasmin copper and specific oxidase activity of the ceruloplasmin (activity per gram) were unchanged. A highly significant relationship was found between gamma-glutamyltransferase and (a) copper (r = 0.682, p less than 0.001), (b) ceruloplasmin (r = 0.523, p congruent to 0.001), and (c) the oxidase activity of the ceruloplasmin (r = 0.598, p less than 0.001). There is also a significant correlation of hemopexin with ceruloplasmin (r = 0.531, p congruent to 0.001) and the oxidase activity of the ceruloplasmin (r = 0.598, p less than 0.001). These results suggest that hypercupremia in patients undergoing long-term anticonvulsant therapy is a direct result of hepatic enzyme induction caused by the drugs that induce synthesis of ceruloplasmin.