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Autoinduction and steady‐state pharmacokinetics of carbamazepine and its major metabolites.

1992; Wiley; Volume: 33; Issue: 6 Linguagem: Inglês

10.1111/j.1365-2125.1992.tb04089.x

1365-2125

TB Kudriakova, Sirota La, G.I. Rozova, V.A. Gorkov,

Metabolism and Genetic Disorders

1. The effect of carbamazepine (CBZ) dose change on mean plasma concentrations of CBZ, its two metabolites and apparent steady‐state clearance was studied in 77 affectively ill patients receiving CBZ at doses of 100‐1200 mg day‐1. 2. Autoinduction of CBZ metabolism appeared to be complete within 1 week of starting CBZ therapy or dose change, and its degree was linearly related to CBZ daily dose. 3. Curvilinear plots were obtained for steady‐state concentrations of CBZ and its ‐ 10,11‐epoxide metabolite, and for the ratio of CBZ‐10,11‐epoxide to CBZ level, versus daily dose of CBZ. 4. On the contrary, steady‐state concentration of CBZ‐10,11‐diol increased proportionately with the dose. This indicates that there is no dose dependency in absorption of CBZ, and that dose‐dependent autoinduction of CBZ metabolism is the main cause of the curvilinear relationship between dose and steady‐ state concentration of CBZ and its intermediary metabolite, CBZ‐10,11‐ epoxide.