Zinc and Copper Metabolism in Phenytoin Therapy

Abstract

The effect of phenytoin (PHT) on the metabolism of zinc (Zn) and copper (Cu) has been studied during treatment for epilepsy. Eleven previously untreated epileptics were followed from the start of therapy together with 20 patients on long-term therapy. In eight untreated epileptic males low serum concentrations of Zn (S-Zn) were found. At the start of therapy increased S-Zn and S-Cu concentrations were noted. After 1 month of therapy S-Zn was at pretherapy levels but S-Cu was still increased. No changes in the urinary excretion of the metals or in the CSF-Zn concentrations were registered. In the patients on long-term therapy S-Zn was unchanged while S-Cu and S-ceruloplasmin were increased significantly compared with age- and sex-matched controls. It is postulated that the drug may cause a relative zinc deficiency through a chelate binding between Zn and PHT and/or an increased absorption and accumulation of Cu. These effects may be of importance in the development of intoxication symptoms and may also influence the effectiveness of seizure control.

Serum Zinc Levels in Children With Simple Febrile Seizure

“…4 Thus, in hypozincemia these N-methyl-D-aspartate receptors get activated, inducing an epileptic discharge in febrile children. Low serum and CSF zinc concentrations have been reported in patients with epilepsy 5 and hepatic encephalopathy 6 and in babies with a benign seizure disorder that occurs on the fifth day of life. 7 In our study, serum zinc levels in children with febrile seizure were lower than in children who had only fever, thus indicating that zinc deprivation plays a role in the pathogenesis of febrile seizure.…”

Genetically Epilepsy‐Prone Rats are Characterized by Altered Tissue Trace Element Concentrations

“…In addition to alterations in manganese, low plasma zinc (Barbeau and Donaldson, 1974), and elevated plasma copper (Brunia and Buyze, 1972) have been reported in epileptic adult humans. In contrast to manganese, however, the copper abnormality has been suggested to be due to AED therapy (Palm and Hallmans, 1982;Taylor and Ghose, 1986;Werther et al, 1986) and that the low plasma zinc may be an experimental artifact (Vasiliades and Sahawneth, 1975;Ghose and Taylor, 1983;Carl et al, 1987).…”

Anti-neutrophil antibodies in patients with nutritional copper deficiency

“…These observations suggest that the production of ANA might be (intracellular) copper dependent. Anti convulsants may alter copper metabolism [10], but cases 2-7 did not receive such medication. With copper supplementation the neutrophil count was normalized and ANA production became negative in patients with a severe deficiency, thus a direct relationship has to be considered.…”