Abstract
A combination of anti‐epileptic drugs is used for the necessary control of seizures. This results in a modulation of the metabolism in the epileptic patient and a concentration of the drugs and their metabolites in serum and in the brain, the target organ. Carbamazepine‐10,11 epoxide (CBZE) is the main active metabolite of carbamazepine (CBZ). We have studied their interrelationship in concentrations in the plasma of 68 patients receiving CBZ, either as monotherapy or in combination with phenytoin (PHT) and phenobarbital (PB). The rate of CBZ metabolism was modulated in drug co‐administration, which, depending on the grade of the induction of cytochrome p‐450, decreases or increases the concentration of CBZE. A graph plotting the relationship between CBZ and CBZE concentrations in patients stabilized on a regime of CBZ alone is linear. The ratio of concentrations of CBZE/CBZ in serum is 0.12 when CBZ is administered as monotherapy, rising to 0.14 (CBZ + PB), 0.18 (CBZ + PHT) and 0.25 (CBZ + PHT + PB) when administered with the other drugs mentioned. From this it can be hypothesized that the additive of induction activities of PHT and PB operates on the mixed function oxidase system.
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