Abstracts

The aim of this retrospective study was to investigate the influence of carbamazepine substitution by oxcarbazepine on lamotrigine serum concentrations in patients with partial seizures.
Lamotrigine is a new anti-epileptic often given as an add-on drug in epileptic patients with partial seizures and treatment-resistant epilepsies. The pharmacokinetic of lamotrigine is linear but complicated by interactions with polypharmacy. Thus, in patients taking hepatic enzyme-inducing drugs, notably carbamazepine, its elimination half-life is reduced.
Oxcarbazepine is likewise a new anti-epileptic drug chemically related to carbamazepine with a very similar efficacity. However, oxcarbazepine is less likely to have pharmacokinetic interactions with lamotrigine.
These observations prompted us to explore the variation of lamotrigine serum concentrations after carbamazepine substitution by oxcarbazepine in patients with partial seizures. More, we examined if this substitution has been associated with a clinical gain.
All patients treated by lamotrigine for partial seizures and for whom carbamazepine had been substituted by oxcarbazepine have been evaluated (n=17).
The lamotrigine doses, the lamotrigine serum concentrations before and after the substitution, and the oxcarbazepine doses were noted.
For each patient, we took notice of the age, the polypharmacy and the number of seizures before and after the substitution. Patients were defined as responders when they showed a reduction in seizures frequency of at least 90%.
To evaluate the specific influence of the substitution, we analysed the data of a control group (n=18). In this group, epileptic patients were treated by oxcarbazepine in comedication, but without lamotrigine.
We first observed that 35% of patients who were co-treated by lamotrigine+oxcarbazepine were responders, while only 5% were responders in the control group (*[italic]P[/italic][lt]0.05).
Moreover, we observed that serum concentrations of lamotrigine evaluated in responders were significantly higher (+63%) than those of non-responders (*[italic]P[/italic][lt]0.05).
Carbamazepine substitution by oxcarbazepine significantly increased the lamotrigine serum concentrations (+57%) (*[italic]P[/italic][lt]0.05). However, this up-regulation was not correlated with the clinical gain.
In this retrospective study,we have observed :
[bull]a clinical gain after carbamazepine substitution by oxcarbazepine
[bull]this gain was more important in patients who were co-treated by lamotrigine + oxcarbazepine than in the control group
[bull]the lamotrigine serum concentrations were significantly higher in responders
[bull]the substitution significantly increased the lamotrigine serum concentrations. This up-regulation was not correlated with the clinical gain. However, lamotrigine serum concentrations were higher in responders ; it is therefore possible that the number of evaluated patients was not suffisant to reveal a significant difference between responders and non-responders.