LYMPHOCYTE MICROSOMAL EPOXIDE HYDROLASE IN PATIENTS ON CARBAMAZEPINE THERAPY

1 In order to determine whether carbamazepine is an inducer of lymphoc yte microsomal epoxide hydrolase, the activity of the enzyme has been measured in the lymphocytes of 40 patients on continuous drug therapy using [H-3]-cis stilbene oxide as a substrate. 2 Induction of the cyto chrome P450 isoform, CYP3A, has been assessed in the same patients by measurement of the 24 h urinary excretion of 6 beta-hydroxycortisol by radioimmunoassay. The urinary concentrations of carbamazepine and its two metabolites, the 10,11-epoxide and trans-dihydrodiol, have also b een measured by h.p.l.c. 3 The 24 h urinary 6 beta-hydroxycortisol exc retion in the patients increased with the dose of carbamazepine (r = 0 .57, P < 0.001) indicating induction of CYP3A. 4 The total amount of t rans-dihydrodiol excreted in the urine increased with the dose of carb amazepine, and it was the most abundant urinary metabolite in all pati ents and at all dose-levels. There was no relationship between the dos e of carbamazepine and the diol to epoxide ratio (r = -0.01, NS). 5 Ly mphocyte microsomal epoxide hydrolase activity was marginally, but sig nificantly (P = 0.02) higher in the patients (28.4 pmol diol min(-1) m g(-1) protein) than in drug-free controls (23.4 pmol diol min(-1) mg(- 1) protein (95% CI for difference -9 to -0.8)). 6 The results indicate that at concentrations of carbamazepine which produce marked inductio n of hepatic CYP3A, an enzyme involved in the metabolism and bioactiva tion of carbamazepine, there is only a slight increase in lymphocyte m icrosomal epoxide hydrolase.