Pharmacokinetic variability of eslicarbazepine in real clinical practice

Abstract

INTRODUCTION\nEslicarbazepine acetate (ESL) is a sodium channel blocker indicated for partial-onset seizures with or without secondary generalization, at a single daily dose. There are very few publications on the levels of ESL metabolites in real clinical practice.\n\n\nOBJECTIVE\nTo describe the serum levels of licarbazepine (main metabolite of ESL) in patients with refractory epilepsy in real clinical practice. To evaluate the influence of age, sex, and polytherapy on levels and adverse effects.\n\n\nMETHODS\nThis study involved a retrospective analysis of patients diagnosed with epilepsy treated with ESL for whom plasma levels of licarbazepine were available, measured by spectrophotometry.\n\n\nRESULTS\nSixty-four patients were included. One patient had licarbazepine levels of 0 (admitted not taking the drug) was not analyzed. Mean licarbazepine levels of 7.66\u202fµg/mL (400\u202fmg/day dose), 16.56\u202fµg/mL (800-mg dose), and 20.80\u202fµg/mL (1200\u202fmg) were significantly different. There was a significant correlation between daily dose and serum levels (p\u202f<\u202f0.05) and between the concentration/dose ratio and lower to higher doses (p\u202f<\u202f0.05). Pharmacokinetic variability (coefficient of variation for the concentration/dose ratio) was 33.2%. We found a decrease in the concentration/dose ratio in the 1200\u202fmg/day dose, compared to lower doses. We did not find differences by sex or intake of other antiepileptic inducers or metabolic inhibitors. Fifteen patients (23.8%) had mild nonsymptomatic hyponatremia.\n\n\nCONCLUSION\nThese results suggest that it is not necessary to routinely determine licarbazepine levels. In specific cases, licarbazepine levels can be useful to assess adherence to treatment and for personalized dose adjustment.