The effects of chronic drug administration on hepatic enzyme induction and folate metabolism.

1 Patients on prolonged treatment with anticonvulsant and phenothiazine drugs exhibited lower than normal concentrations of folate in serum and erythrocytes, and showed increased urinary FIGLU excretion after histidine loading; urinary excretion of D-glucaric acid was also increased suggesting induction of the hepatic microsomal enzymes. 2 Folate deficiency by enzyme-inducing drugs was seen to be determined more by the duration of therapy than by the nature of the drugs. Excretion of FIGLU was increased by 70% by 2-5 years of treatment with anticonvulsant, phenothiazine or tricyclic drugs, and by 200% after 6 or more years. 3 Hepatic microsomal enzyme induction, as measured by D-glucaric acid excretion, was greatest after 2-5 years treatment. 4 It is suggested that the increased requirements for folate, resulting from microsomal enzyme induction, lead to folate deficiency and this subsequently limits enzyme induction, leading to adverse drug side-affects. 5 The dietary folate of hospitalized patients would seem to be generally inadequate for patients on long term treatment with enzyme-inducing drugs.