Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction

Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route.

Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity.

This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis.

After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods.

To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.