PHARMACOKINETIC BEHAVIOR OF CARBAMAZEPINE AND ITS MAIN METABOLITE-10,11 EPOXIDE OF CARBAMAZEPINE IN MONOTHERAPY OR IN COMBINATION WITH OTHER ANTIEPILEPTIC DRUGS

A combination of anti-epileptic drugs is used for the necessary contro l of seizures. This results in a modulation of the metabolism in the e pileptic patient and a concentration of the drugs and their metabolite s in serum and in the brain, the target organ. Carbamazepine-10,11 epo xide (CBZE) is the main active metabolite of carbamazepine (CBZ). We h ave studied their interrelationship in concentrations in the plasma of 68 patients receiving CBZ, either as monotherapy or in combination wi th phenytoin (PHT) and phenobarbital (PB). The rate of CBZ metabolism was modulated in drug coadministration, which, depending on the grade of the induction of cytochrome p-450, decreases or increases the conce ntration of CBZE. A graph plotting the relationship between CBZ and CB ZE concentrations in patients stabilized on a regime of CBZ alone is l inear. The ratio of concentrations of CBZE/CBZ in serum is 0.12 when C BZ is administered as monotherapy, rising to 0.14 (CBZ + PB), 0.18 (CB Z + PHT) and 0.25 (CBZ + PHT + PB) when administered with the other dr ugs mentioned. From this it can be hypothesized that the additive of i nduction activities of PHT and PB operates on the mixed function oxida se system. Eur J Neurol 5:397-400 (C) 1998 Lippincott-Raven Publishers .