Clinical pharmacology of cannabidiol in refractory epilepsy.

Objective: The aim of this article is to provide a systematic and updated review  on the pharmacology of cannabidiol in the context of refractory epilepsy, with  special emphasis on its pharmacokinetics, adverse drug reactions and drug-drug interactions.

Method: A review of the literature related to cannabidiol pharmacokinetics, adverse drug reactions and drug-drug interactions was  carried out in the context of refractory epilepsy, through a search in PubMed and LILACS.

Results: Original studies that exhaustively describe the pharmacokinetics of  cannabidiol are limited but informative. Cannabidiol is rapidly absorbed and its  bioavailability increases when administered with high fat meals. Cannabidiol  exhibits a linear pharmacokinetic profile for doses up to 3,000 mg/day and  accumulates after multiple administrations. Elimination half-life has been  reported between 14 h and 60 h depending on the sampling times of each  study; changes in cannabidiol elimination due to continuous administration  cannot be discarded. Of all reported drugdrug interactions with anticonvulsants  or other co-administered drugs in patients with epilepsy, the strongest evidence  is provided with clobazam. The most frequent cannabidiol-related adverse drug  reactions were low to moderate and included somnolence, mainly related to  concomitant administration of clobazam, and gastrointestinal alterations. Also,  liver function abnormalities were reported during the use of cannabidiol and valproic acid.

Conclusions: Given the increased use of cannabidiol in refractory epilepsy, a  comprehensive understanding of its pharmacological profile is essential for the  clinical team. Specifically, clinical pharmacists play an important role in  monitoring cannabidiol's safety and efficacy. This approach leads to treatment  optimization, allowing to maximizing the pharmacological activity and minimizing the occurrence of adverse events as well as drug-to-drug interactions. Clinical  follow-up is essential to avoid discontinuation of treatment or exacerbation of  adverse events, which may impair the patients' quality of life.