Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children

Abstract

1 Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication.

2 This study was performed to assess the pharmacokinetic profile of lamotrigine in three groups of children treated with different types of comedication: drugs known to induce, to inhibit or to have no clinically significant influence on drug metabolism, respectively.

3 Thirty-one children aged 6 months to 5 years were included and received a 2 mg kg⁻¹ single oral dose. Lamotrigine plasma profiles were different between the three comedication groups. The half-lives (mean±s.d.) were: 7.7±1.8 h, 21.9±6.8 h, 44.7±10.2 h in the ‘inducer’, ‘other’ and ‘inhibitor’ groups respectively.

4 Patients were then dosed to steady state, with the dosage adjusted on the basis of the single dose pharmacokinetics to achieve a minimum plasma concentration between 1.5 and 3 mg l⁻¹. The mean minimum plasma concentration for the three groups was 2.54±1.28 mg l⁻¹ at steady state.

5 Dosage of lamotrigine can be optimised with knowledge of the metabolic effects of antiepileptic comedication.

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