Relationship of Intraindividual Dose to Plasma Concentration of Carbamazepine; Indication of Dose-Dependent Induction of Metabolism

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Abstract
The effect of a dose change on the plasma concentration of carbamazepine (CBZ) was studied in 13 epileptic patients, all with a CBZ dose of at least 800 mg/day. A disproportionately small rise in the plasma concentration of CBZ was found in 10 of the patients. The ratio between the final metabolite 10,11-dihydro-10,11-trans-dihydroxy-CBZ and CBZ in plasma was higher after dose increase in the 10 patients with a small rise in CBZ levels, indicating a dose-dependent autoinduction of CBZ metabolism. The ratio between the active intermediary metabolite, CBZ-epoxide, and CBZ was unaltered by the dose change in all patients. This indicates that CBZ plasma level determinations can be used for prediction of the total effect of CBZ treatment during high as well as low dosage.

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