Topiramate, Serum or Plasma

Topiramate is an anticonvulsant drug used as an adjunctive therapy in the treatment of patients with partial and secondary generalized epilepsy. Topiramate is a sulfamate-substituted monosaccharide, derived from D-fructose. The animal models suggest that topiramate exerts its anticonvulsant effect primarily by blocking the spread of seizures, rather than by elevating the seizure threshold. Pharmacokinetic studies in humans have shown that topiramate is absorbed rapidly, excreted largely unchanged in the urine.¹ Carbamazepine and phenytoin can significantly induce the metabolism of topiramate, whereas valproic acid has only a slight influence on topiramate concentrations.² The elimination half-life of topiramate is 18 to 23 hours and is dose-dependent; however, children, as differentiated from adults, can require at least a twofold increase in dose to achieve a comparable plasma level.³ The drug is approximately 15% protein bound. Although carbamazepine and phenytoin induce the metabolism of topiramate and shorten its half-life, topiramate has no significant effect on the plasma concentrations of these drugs or valproic acid. Maintenance doses of topiramate, given twice daily, range from 300−600 mg/day. Side effects include dizziness, reduced cognitive function, weight loss, and headache. As observed with many therapeutic agents, the interpatient variability in clinical response at similar topiramate plasma concentration can be appreciable. Differences in plasma levels between responders, nonresponders, and seizure-free patients can be indiscernible.