Pharmacokinetic interactions between lamotrigine and other antiepileptic drugs in children with intractable epilepsy

Purpose: We wished to determine the oral pharmacokinetics of lamotrigine LTG and to assess possible interactions with other AEDs in an unselected population of children. Concentration data in plasma and in CSF for lamotrigine as well as for the other AEDs are presented. Methods: Thirty-one children, children and young adults aged >2 years with intractable generalized epilepsy despite adequate duration and dose of at least three conventional AEDs were studied. Results: There was a linear relation between the dose administered and the maximal plasma concentration, indicating that saturation of absorption or elimination mechanisms did not occur in the dose range studied. The median elimination half-life (t1/2) in patients receiving concomitant valproate (VPA) was 43.3 h; in patients receiving carbamazepine (CBZ) and/or phenobarbital (PB), it was 14.1 h; and in patients receiving both VPA and CBZ/PB or other antiepileptic drugs (AEDs), it was 28.9 h, No clinically important changes in the plasma levels of CBZ, VPA, valproate, ethosuximide, or PB were observed in the follow-up period (2-12 months). No dose adjustments of concomitant AEDs were necessary. The plasma concentration of clonazepam (CZP) was reduced when LTG was introduced. Conclusions: The complex interaction between LTG and other AEDs in children with intractable epilepsy makes therapeutic drug monitoring (TDM) desirable.