Effect of Lamotrigine on Carbamazepine Epoxide/carbamazepine Serum Concentration Ratios in Adult Patients with Epilepsy

Although lamotrigine (LTG) appears to have a low propensity to cause pharmacokinetic interactions with other medications, it has been suggested that LTG may interfere with the elimination of carbamazepine 10,11-epoxide (CBZE), the active metabolite of carbamazepine (CBZ). Evidence for this pharmacokinetic interaction is inconclusive and conflicting, however. We evaluated CBZ apparent oral clearance and the steady-state CBZE/CBZ serum concentration ratios in nine patients (30.8 +/- 7.7 years) with epilepsy prior to and following the initiation of adjunctive treatment with LTG. Overall, CBZ oral clearance was unchanged following the introduction of LTG (5.58 +/- 1.60 vs. 5.81 +/- 1.74 1/h, P = 0.630). Likewise, CBZE to CBZ serum concentration ratios were not significantly different (0.241 +/- 0.082 vs. 0.232 +/- 0.082, P = 0.782). These observations suggest that the addition of LTG did not result in a significant pharmacokinetic interaction involving either CBZ or CBZE.