THE INFLUENCE OF DOSAGE, AGE, AND COMEDICATION ON STEADY-STATE PLASMALAMOTRIGINE CONCENTRATIONS IN EPILEPTIC CHILDREN - A PROSPECTIVE-STUDY WITH PRELIMINARY ASSESSMENT OF CORRELATIONS WITH CLINICAL-RESPONSE

The effects of age, dosage, and type of comedication on plasma lamotri gine (LTG) concentrations and the relationship between plasma drug lev els and clinical response were evaluated in a prospective study of 45 patients, aged 3 to 38 years, with epilepsy uncontrolled by convention al anticonvulsant therapy. Six of the 45 patients were on single-drug therapy, and 39 were on two to five concurrently administered antiepil eptic drugs when LTG was added, Thirteen patients were assessed at thr ee or more LTC dosage levels. Within individuals, steady state plasma LTG concentrations increased linearly with increasing daily dosage ove r the examined dose range (25 to 575 mg/day or 0.75 to 21 mg/kg . day) . Among patients also receiving enzyme-inducing agents, such as carbam azepine, barbiturates, or phenytoin, plasma LTG concentrations normali zed to a 1 mg/kg daily dose were lower In children aged 3 to 6 years ( 0.30 +/- 0.17 mu g/ml; n = 6) than in the older children (0.43 +/- 0.1 8 mu g/ml; n = 12) and adolescents/adults (0.68 +/- 0.26 mu g/ml; n = 10). In patients treated with valproate, the age dependency of plasma LTG was less evident, possibly because of a smaller sample size and th e confounding effect of comedication, Within any given age group, dose -normalized LTG concentrations were about five-fold higher in patients comedicated with valproic acid than in those comedicated with enzyme inducers, Twenty patients showed a favorable response (with a greater than or equal to 40% reduction in seizure frequency compared with the pre-LTG period) and continued on long-term treatment, Plasma drug conc entrations in these apparent responders were highly variable and did n ot differ significantly from those observed in nonresponders (6.6 +/- 5.2 versus 4.8 +/- 3.3 mu g/ml). These findings show that plasma LTG c oncentrations exhibit a wide interindividual variability under the inf luence of age and type of comedication, but they are predictably relat ed to dosage within individual patients, Although there was no apparen t relationship between drug levels and clinical response in this diffi cult-to-treat population, further studies on the potential value of mo nitoring plasma LTG concentrations are indicated.