<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1130-6343</journal-id>
<journal-title><![CDATA[Farmacia Hospitalaria]]></journal-title>
<abbrev-journal-title><![CDATA[Farm Hosp.]]></abbrev-journal-title>
<issn>1130-6343</issn>
<publisher>
<publisher-name><![CDATA[Grupo Aula Médica]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1130-63432020000500006</article-id>
<article-id pub-id-type="doi">10.7399/fh.11390</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Clinical pharmacology of cannabidiol in refractory epilepsy]]></article-title>
<article-title xml:lang="es"><![CDATA[Farmacología clínica de cannabidiol en epilepsias refractarias]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Schaiquevich]]></surname>
<given-names><![CDATA[Paula]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Riva]]></surname>
<given-names><![CDATA[Natalia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Maldonado]]></surname>
<given-names><![CDATA[Cecilia]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vázquez]]></surname>
<given-names><![CDATA[Marta]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cáceres-Guido]]></surname>
<given-names><![CDATA[Paulo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Hospital de Pediatría JP Garrahan Precision Medicine ]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,National Scientific and Technical Research Council  ]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad de La República School of Chemistry Pharmaceutical Science Department]]></institution>
<addr-line><![CDATA[Montevideo ]]></addr-line>
<country>Uruguay</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Pharmacy, Hospital de Pediatría JP Garrahan Unit of Clinical Pharmacokinetics ]]></institution>
<addr-line><![CDATA[Buenos Aires ]]></addr-line>
<country>Argentina</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>10</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>10</month>
<year>2020</year>
</pub-date>
<volume>44</volume>
<numero>5</numero>
<fpage>222</fpage>
<lpage>229</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_arttext&amp;pid=S1130-63432020000500006&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_abstract&amp;pid=S1130-63432020000500006&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_pdf&amp;pid=S1130-63432020000500006&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  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 drug-drug 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&#8217;s safety and ef&#64257;cacy. 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&#8217; quality of life.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen  Objetivo: El objetivo del presente trabajo es brindar una revisión sistemática y actualizada acerca de la farmacología de cannabidiol, con especial énfasis en la farmacocinética, eventos adversos e interacciones, vinculada al uso de este fármaco en epilepsias refractarias.  Método: Se realizó una revisión de los trabajos publicados y relacionados con la farmacocinética y los eventos adversos e interacciones farmacológicas de cannabidiol utilizado para el tratamiento de las epilepsias refractarias mediante una búsqueda en PubMed y LILACS.  Resultados: Los estudios originales que describen la farmacocinética de cannabidiol de manera exhaustiva son limitados aunque informativos. La absorción de cannabidiol es rápida y se incrementa la biodisponibilidad por la ingesta conjunta de comidas ricas en grasas. El cannabidiol presenta farmacocinética lineal hasta dosis de 3.000 mg/día y se acumula por la administración continua. La semivida de eliminación se referencia entre 14 y 60 horas dependiendo de los tiempos de toma de muestra del estudio farmacocinético y no se descartan modificaciones en la eliminación por la administración en dosis múltiples. De las interacciones farmacológicas entre cannabidiol con otros fármacos antiepilépticos referenciadas hasta el momento, aquella con clobazam es la que presenta mayor evidencia científica. Los eventos adversos más frecuentes asociados al uso de cannabidiol fueron de gravedad leve o moderada e incluyeron somnolencia, principalmente por el uso conjunto de clobazam, y alteraciones gastroin testinales. Se evidenciaron asimismo anormalidades en la función hepática concomitantes con el uso de ácido valproico.  Conclusiones: Ante la creciente demanda de la utilización de cannabidiol en epilepsias refractarias, es fundamental el conocimiento de su farmacología por parte del equipo de salud. En especial, el farmacéutico clínico juega un papel primordial en la monitorización de su seguridad y eficacia. Esto permite la optimización del tratamiento clínico del cannabidiol administrado conjuntamente con otros fármacos antiepilépticos de mayor uso, lo que conduce a maximizar la actividad farmacológica y minimizar la aparición de eventos adversos al igual que de interacciones farmacológicas. El seguimiento clínico del paciente resulta fundamental para evitar la discontinuación del tratamiento o exacerbación de eventos adversos que afecten la calidad de vida del paciente.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Cannabidiol]]></kwd>
<kwd lng="en"><![CDATA[Pharmacokinetics]]></kwd>
<kwd lng="en"><![CDATA[Drug resistant epilepsy]]></kwd>
<kwd lng="en"><![CDATA[Adverse drug reactions]]></kwd>
<kwd lng="en"><![CDATA[Drug interactions]]></kwd>
<kwd lng="es"><![CDATA[Cannabidiol]]></kwd>
<kwd lng="es"><![CDATA[Farmacocinética]]></kwd>
<kwd lng="es"><![CDATA[Epilepsia refractaria]]></kwd>
<kwd lng="es"><![CDATA[Eventos adversos a fármacos]]></kwd>
<kwd lng="es"><![CDATA[Interacciones farmacológicas]]></kwd>
</kwd-group>
</article-meta>
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