Lack of an effect of topiramate on lamotrigine serum concentrations

Purpose: Pharmacokinetic interactions between the older antiepileptic drugs (AEDs) and topiramate (TPM) were assessed during the clinical development of this drug. Lamotrigine (LTG) has become established as an important new drug in treating a wide spectrum of seizure types, but there are no published data on whether LTG serum concentrations change when TPM is added to treatment. Methods: Escalating doses of TPM were added to stable LTG treatment in 24 young patients (8-21 years) with epilepsy. Blood samples taken before the morning dose were collected for drug-concentration measurement in all patients before starting treatment with TPM and after stabilisation at each dose escalation. Several patients had been maintained on unchanged therapy with drug-concentration monitoring for many months before introducing TPM, and a sequence of baseline LTG serum concentrations were available on these patients. Results: The mean of all baseline LTG concentrations for the group as a whole was 10.4 +/- 4.4 mg/L compared with 9.7 +/- 4.3 mg/L after addition of TPM. A comparison of last baseline LTG concentration with first test LTG concentration (i.e., after 2 weeks' TPM treatment) gave mean values of 10.7 +/- 4.7 and 10.8 +/- 4.6 mg/L, respectively. The mean LTG concentration for patients while taking their highest TPM dose was 9.5 +/- 4.3 mg/L. The analysis-of-variance modeling for the effect of TPM on LTG concentration yielded a mean LTG concentration ratio (with TPM vs. without TPM) of 94.2%, with a 90% confidence interval of 89.5-99.1%. Conclusions: TPM did not cause a significant change in LTG serum concentration in this group of patients.