Carbamazepine seems to as effect as
phenytoin in the treatment of grand mal and
psychomotor epilepsy. It is the
drug of first choice in
trigeminal neuralgia. After single oral doses of
carbamazepine, the absorption is fairly complete and the elimination half-life is about 35 hours (range 18 to 65 hours). During multiple dosing, the half-life is decreased to 10-20 hours, probably due to autoinduction of the oxidative metabolism of the
drug.
Phenytoin and
barbiturates also induce the metabolism of
carbamazepine. After single doses of
carbamazepine, elimination follows dose-dependent first order kinetics.
Carbamazepine is metabolised by oxidation before excretion in the urine. In experimental animals, the metabolite
carbamazepine-10,11-epoxide has
anticonvulsant activity comparable with that of the parent
drug. The plasma concentration of the metabolite during long-term treatment of epileptic patients varies between 5 and 81% of that of the parent
drug. The
plasma protein binding of the metabolite is about 50% compared with about 75% for the parent
drug. Less than 50% of a given
carbamazepine doses has been identified as metabolites in the urine. The quantitatively most important metabolites is the trans-10,11-dihydro-10,11-diol. The kinetics of
carbamazepine have been explored to some extent in pregnant women, newborns and children. Plasma levels of
carbamazepine seem to decrease during pregnancy, possibly as a result of increased metabolism. The
drug readily crosses the placenta and the levels measured in newborns are comparable with maternal plasma concentrations. In newborns exposed to the
drug during fetal life, the plasma half-lives were relatively short (8.2 to 28.1 hours) indicating an induction of
carbamazepine metabolism during gestation. The pharmacokinetics of
carbamazepine in children aged 0.3 to 15 years are comparable with that in adults. A single daily dose of
carbamazepine is insufficient; 2 doses per day are appropriate in most cases, but some patients may benefit from more frequent dosing to avoid side-effects. Compared with
phenytoin, for example, very few controlled studies have been performed to establish the plasma level range of
carbamazepine associated with the best therapeutic outcome. However, the best
anticonvulsant effect of
carbamazepine seems to be obtained at plasma levels of about 5 to 10microgram/ml (20 to 40mumol/L). Side-effects are most frequent at higher levels but may also be seen at lower levels.