Introduction: Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route.
Objectives: 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.
Methods: 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.
Results: 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.
Conclusion: To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.
Keywords: High dimensional data; Penalized regression; Personalized medicine; Zonisamide metabolomics.