Lamotrigine serum concentration-to-dose ratio : Influence of age and concomitant antiepileptic drugs and dosage implications

Using bivariate and multivariate methods, we retrospectively analyzed the influence of patient age and the use of concomitant antiepileptic drugs (AEDs) on the lamotrigine (LTG) concentration-to-dose (C/D) ratio in samples from 164 patients (68 children, 96 adults) with epilepsy receiving LTG alone (n = 28) or in combination with various antiepileptic drugs (n = 136). The LTG C/D ratio increased with age in children receiving LTG alone (r = 0.60, p < 0.01), but decreased with age in adults receiving LTG and inducers (r = -0.42, p < 0.001). In patients receiving LTG and inducers, the ratio was statistically lower in those younger than 9 years of age (0.23 +/- 0.08) and older than 30 years of age (0.32 +/- 0.15) than it was in those between 9 and 30 years of age (0.44 +/- 0.15). The mean LTG C/D ratio was 0.37 +/- 0.15 in patients receiving LTG and inducers (n = 92), 0.84 +/- 0.41 in patients receiving LTG alone (n = 28), 1.09 +/- 0.44 in those receiving LTG with VPA plus inducers (n = 17), and 3.41 +/- 1.18 in those receiving LTG and VPA (n = 27). Differences in the LTG C/D ratio between treatment groups were similar in children and in adults. We reached the following conclusions: The LTG C/D ratio increased with age in children but may decrease with age in adults receiving concomitant enzyme-inducing AEDs; the LTG C/D ratio was 10 times lower in patients receiving LTG and inducers than in those receiving LTG and VPA (in both children and adults), and this difference was higher than the four-fold difference described for LTG half-life and the two-fold differences currently used in LTG dosage.