Therapeutic Drug Monitoring of Ethosuximide.

Therapeutic Drug Monitoring of Ethosuximide. Ethosuximide is a minor antiepileptic drug, available in France since 1965, indicated in the epilepsy absence, whose interest was reassessed from recent clinical trials, showing that it was the first choice, in term of risk benefit relationship, in this indication. It is a chiral molecule that presents a high bioavailability, a lack of protein binding, hepatic metabolism and urinary excretion. Its elimination half-life is long, between 40 and 60 h in adults, 30 and 40 h in children. The therapeutic range is established at 40-100 mg/L (283-708 pmol/L), but the upper limit is probably underestimated. The clinical studies of relation exposure effects, although ancient (from the 1970s) and realized with methodologies that do not meet current criteria, show concentration-efficacy and -toxicity relationship and the risk of drug interactions is proven. It is a drug preponderantly prescribed in children, a vulnerable population with physiological change with age. To benefit at best of its effectiveness, it is necessary to have relatively high plasma concentrations. Despite these arguments and due to the lack of studies providing a sufficient level of evidence, the recommendation can only be potentially useful, assessment probably underestimated.