The impact of <i>Paullinia cupana</i> extract on pharmacokinetics of phenytoin in rats

Epilepsy patients are at a higher risk of developing overweight and obesity. Given the thermogenic properties of <i>Paullinia cupana</i> (Guarana), this study aimed to evaluate a potential pharmacokinetic interaction between <i>P. cupana</i> extract and phenytoin in rats. Two pharmacokinetic studies were developed with <i>P. cupana</i> and phenytoin: a coadministration and a pre-treatment study. Plasma concentrations of phenytoin and its primary metabolite (5-(4-hydroxyphenyl)-5-phenylhydantoin) were determined by HPLC-DAD, and data were analysed by non-compartmental pharmacokinetic methods. Both studies demonstrated a significant delay in the time to reach peak plasma concentration of phenytoin and its primary metabolite. Furthermore, a lower extent of systemic exposure of its primary metabolite was found in the coadministration study. In addition, the pre-treatment study indicated weight loss in the experimental group. These results suggest that concurrent administration of <i>P. cupana</i> extract with phenytoin may compromise the drug's therapeutic efficacy.