Safety evidence on the administration of Fucus vesiculosus L. (bladderwrack) extract and lamotrigine: data from pharmacokinetic studies in the rat.

Fucus vesiculosus is often incorporated in weight loss dietary supplements to improve weight loss in overweight adults. Obesity is a common condition in epilepsy patients and is indeed increasing in refractory epilepsy and in patients under polytherapy. Since lamotrigine (LTG) is a first-line antiepileptic drug, used in monotherapy or adjunctive therapy, the main objective of this work was to investigate the potential pharmacokinetic-based interactions between F. vesiculosus and LTG in rats. In a first pharmacokinetic study, a single oral dose of F. vesiculosus extract (575 mg/kg, p.o.) was co-administered with a single-dose of LTG (10 mg/kg, p.o.). In a second study, rats were orally pretreated with F. vesiculosus extract (575 mg/kg/day, p.o.) for 14 days and received LTG (10 mg/kg, p.o.) on the 15th day. In the control groups, rats received water instead of the extract. After LTG administration, blood samples were taken until 96 h post-dose, and LTG concentrations measured in plasma were submitted to a non-compartmental pharmacokinetic analysis. The co-administration of F. vesiculosus extract and LTG caused no significant changes in the drug kinetics. However, the repeated pretreatment with F. vesiculosus extract significantly reduced the peak concentrations of LTG and caused a slightly decrease in the extent of systemic drug exposure. Overall, based on these results, no significant clinical impact is expected from the administration of F. vesiculosus dietary supplements and LTG.

Short-term effects of Garcinia cambogia extract on the pharmacokinetics of lamotrigine given as a single-dose in Wistar rats.

Garcinia cambogia supplements are widely used for weight loss. Knowing that epilepsy patients are at greater risk of developing overweight/obesity, the investigation of herb-drug interactions involving antiepileptic drugs of narrow therapeutic index is fully justified. This work was planned to assess potential pharmacokinetic-based interactions between G. cambogia extract and lamotrigine (LTG) through two independent pharmacokinetic studies. In the first study (co-administration study), rats were orally co-administered with a single-dose of G. cambogia extract (821 mg/kg) and LTG (10 mg/kg). In the second study (pre-treatment study), rats were orally pre-treated for 14 days with G. cambogia extract (821 mg/kg/day), being LTG administered (10 mg/kg) on the 15th day. Rats of the control groups received water instead of the extract. Following LTG administration, blood samples were collected until 96 h post-dose, and plasma LTG concentrations were determined and submitted to a non-compartmental analysis. Globally, no statistically significant effects were identified in the co-administration study of G. cambogia extract and LTG. In the 14-day pre-treatment study, a statistically significant decrease in the rate of systemic exposure to LTG and an increase of apparent volume of distribution were found. Even so, a minor or no clinical impact is expected from the administration of G. cambogia dietary supplements and LTG.

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

Citrus aurantium extracts 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 of C. aurantium extract on the pharmacokinetics of lamotrigine (LTG) in rats. In the first pharmacokinetic study, a single oral dose of C. aurantium extract (164 mg/kg; p.o.) was administered with a single oral dose of LTG (10 mg/kg; p.o.). In the following study, the C. aurantium extract 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 of C. aurantium extract 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 < 0.05). Considering the minor effects induced by C. aurantium extract on the pharmacokinetics of LTG in rats, no relevant interactions are expected to occur in the clinical practice. Notwithstanding, C. aurantium safety in patients under LTG therapy should be further assessed in controlled clinical trials.