PHARMACOKINETIC INTERACTIONS BETWEEN LAMOTRIGINE AND OTHER ANTIEPILEPTIC DRUGS IN CHILDREN WITH INTRACTABLE EPILEPSY

Purpose: We wished to determine the oral pharmacokinetics of lamotrigi ne LTG and to assess possible interactions with other AEDs in an unsel ected 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 intr actable generalized epilepsy despite adequate duration and dose of at least three conventional AEDs were studied. Results: There was a linea r relation between the dose administered and the maximal plasma concen tration, indicating that saturation of absorption or elimination mecha nisms 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 phenobarbita l (PB), it was 14.1 h; and in patients receiving both VPA and CBZ/PB o r other antiepileptic drugs (AEDs), it was 28.9 h, No clinically impor tant changes in the plasma levels of CBZ, VPA, valproate, ethosuximide , or PB were observed in the follow-up period (2-12 months). No dose a djustments of concomitant AEDs were necessary. The plasma concentratio n 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 .