This study investigates the time course of deinduction of the enzyme CYP3A4 following discontinuation of carbamazepine (CBZ) by measuring plasma concentrations of remacemide (REM), a substrate of the enzyme. Healthy subjects will be treated for 36 days with CBZ to induce the expression of CYP3A4. Administration of REM will begin on Day 22 and will continue through day 57. The ratio of 6-B-hydroxycortisol to cortisol will be used as a measure of induction status. Blood levels of CBZ and REM and their metabolites CBZE and DREM, respectively will be closely monitored through the periods of induction and deinduction. Data will be fit to a monoexponential equation describing the time course of increase of REM following discontinuation of CBZ. These data will aid in timing REM dose reductions necessary to prevent toxicity following discontinuation of CBZ and are applicable to other CYP3A4 substrates coadministered with CBZ.
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