Evaluation of the effects of Citrus aurantium (bitter orange) extract on lamotrigine pharmacokinetics: Insights from in vivo studies in rats

摘要

Citrus aurantiumextracts have thermogenic and lipolytic activities and are largely used for weight loss/management. Once epilepsy and obesity are prevalent comorbid conditions and herb-drug interactions can compromise antiepileptic drugs safety, we aimed to evaluate the effects ofC. aurantiumextract on the pharmacokinetics of lamotrigine (LTG) in rats. In the first pharmacokinetic study, a single oral dose ofC. aurantiumextract (164?mg/kg; p.o.) was administered with a single oral dose of LTG (10?mg/kg; p.o.). In the following study, theC. aurantiumextract was daily administered (164?mg/kg; p.o.) during 14 days followed by a single dose of LTG (10?mg/kg; p.o.) on the 15th day. From the pharmacokinetic analysis, no significant effects were observed after the co-administration ofC. aurantiumextract and LTG. After the 14-day pre-treatment period, the main effects of the extract were limited to a significantly decrease in the time to reach peak drug concentration (tmax;p?