<?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>1134-8046</journal-id>
<journal-title><![CDATA[Revista de la Sociedad Española del Dolor]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. Soc. Esp. Dolor]]></abbrev-journal-title>
<issn>1134-8046</issn>
<publisher>
<publisher-name><![CDATA[Inspira Network Group, S.L ]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1134-80462017000200059</article-id>
<article-id pub-id-type="doi">10.20986/resed.2017.3565/2017</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Paxiflas(r): nueva combinación bucodispersable de tramadol/paracetamol para el tratamiento del dolor moderado a intenso]]></article-title>
<article-title xml:lang="en"><![CDATA[Paxiflas(r): a new combination of tramadol/paracetamol in disintegrating tablets for the treatment of moderate to severe pain]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Tornero-Tornero]]></surname>
<given-names><![CDATA[C.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Galván]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[García]]></surname>
<given-names><![CDATA[I.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Boyer]]></surname>
<given-names><![CDATA[M.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Orduña-Valls]]></surname>
<given-names><![CDATA[J.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Hospital Clínico Universitario de Valencia Servicio de Anestesiología Unidad Dolor]]></institution>
<addr-line><![CDATA[Valencia ]]></addr-line>
</aff>
<aff id="Af2">
<institution><![CDATA[,Laboratorios Gebro Pharma S.A. Departamento Médico ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<aff id="Af3">
<institution><![CDATA[,Athena Drug Delivery Solutions Pvt Ltd Departamento Clínico ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>04</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>04</month>
<year>2017</year>
</pub-date>
<volume>24</volume>
<numero>2</numero>
<fpage>59</fpage>
<lpage>67</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_arttext&amp;pid=S1134-80462017000200059&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_abstract&amp;pid=S1134-80462017000200059&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_pdf&amp;pid=S1134-80462017000200059&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN  Introducción:  Paxiflas(r) es la combinación de clorhidrato de tramadol/paracetamol (37,5 mg/325 mg) en forma de comprimidos bucodispersables de sabor mentolado, comercializado por Laboratorios Gebro Pharma S.A. Los comprimidos bucodispersables se dispersan rápidamente en la boca sin necesidad de agua. Están destinados a pacientes activos que no dispongan de agua en todo momento, personas ocupadas o que viajen con asiduidad. Además, son adecuados en personas con problemas de deglución y ancianos, y favorecen el cumplimiento terapéutico. Además, esta combinación aúna la rapidez de acción del paracetamol con la acción más prolongada del clorhidrato de tramadol.  Objetivos:  Demostrar la bioequivalencia entre los comprimidos bucodispersables de Paxiflas(r), administrados con y sin agua, y los comprimidos de referencia, Zaldiar(r), administrados con agua, en voluntarios sanos en ayunas.  Material y métodos:  Estudio abierto, balanceado, aleatorizado, cruzado, de dosis única, de 3 tratamientos en 3 periodos y 3 secuencias, y con un tiempo de lavado de 7 días entre el periodo I y II y de 8 días entre el II y III. Los voluntarios fueron asignados al azar para recibir una dosis oral única (2 comprimidos) de Paxiflas(r), administrado sin agua (producto A) y con agua (producto B), y Zaldiar(r) con agua. Se consideró bioequivalencia cuando el intervalo de confianza del 90 % (IC 90 %) de la relación de la media geométrica de Cmax and AUC 0-t entre el producto en investigación A o B y el de referencia se encontró dentro del rango 80-12 % para (+) tramadol, (-) tramadol y paracetamol. El objetivo secundario consistió en evaluar la seguridad y tolerabilidad del producto en investigación A y B.  Resultados:  Se evaluó bioequivalencia en 38 voluntarios para el producto A y en 39 para el producto B. Se alcanzaron concentraciones plasmáticas óptimas de (+) tramadol a las 0,75-3 h, para el producto A, a las 0,5-4 h para el B, y a las 0,5-3 h para el de referencia. En el caso del (-) tramadol se alcanzaron a las 0,75-3 h, para el A, a las 0,5-4 h para el B, y 0,5-3 h para el de referencia. Finalmente, para el paracetamol, se alcanzaron a las 0,25-2,5 h para el A, a las 0,5-2 h para el B, y a las 0,25-2,5 h para el de referencia. El IC 90 % de los parámetros principales se situó dentro de los rangos de aceptación del 80-125 % en los 38 voluntarios que tomaron el producto A y en los 39 que tomaron el B. Se reportaron un total de 6 acontecimientos adversos (AA) durante el estudio (dolor de cabeza, mareo, dolor abdominal, picor en antebrazos y muslos, y elevado recuento de eosinófilos), de los que 3 eran esperados y posiblemente relacionados con el producto en investigación. La intensidad de los AA fue desde leve a moderada. No se observó ningún AA grave.  Conclusiones:  Los datos del presente estudio demuestran la bioequivalencia entre los comprimidos bucodispersables de Paxiflas(r), administrados con y sin agua en diferentes periodos, y los comprimidos de Zaldiar(r), administrados con agua, en términos de velocidad y magnitud de la absorción en condiciones de ayuno.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT  Introduction:  Paxiflas(r) is the combination of tramadol HCl/paracetamol (37.5/325 mg) in fast disintegrating tablets (FDTs), commercialized by Laboratorios Gebro Pharma S.A. The FDTs are intended to be placed in the mouth, where they are rapidly disintegrated without the need of water. They are aimed to active patients who do not have access to drinking water all the time, busy individuals, or those who travel frequently. Moreover, they are especially indicated for individuals with difficulties in swallowing and the elderly and help to improve therapeutic compliance. In addition, the combination combines the rapid action of paracetamol with the longer action of tramadol hydrochloride.  Objectives:  To demonstrate the bioequivalence between Paxiflas(r), administered with or without water, and tablets of the reference product, Zaldiar(r), administered with water, in healthy subjects under fasting conditions.  Material and methods:  Open label, balanced, randomized, crossover, single oral dose, 3 treatment, 3 period, 3 sequence, with a washout period of 7 days for subsequent period I and II, and 8 days for period II and III. Subjects were randomized to receive single oral dose (2 tablets) of Paxiflas(r), administered without water (product A) or with water (product B), and Zaldiar(r) with water. Bioequivalence was considered if the 90 % confidence interval (90 % CI) of geometric mean ratio of Cmax and AUC0-t between test and reference product fell within the range of 80-125 % for (+) tramadol, (-) tramadol, and paracetamol. The secondary objective was to monitor the safety and tolerability of products A and B.  Results:  Bioequivalence was evaluated in 38 subjects for product A and in 39 subjects for product B. Optimal plasma concentration levels of (+) tramadol were achieved at 0.75-3 h for product A, at 0.5-4 h for product B, and at 0.5-3 h for reference product. In the case of (-) tramadol, plasma levels were achieved at 0.75-3 h for product A, at 0.5-4 h for product B, and at 0.5-3 h for reference product. Finally, plasma levels of paracetamol were achieved at 0.25-2.5 h for the product A, at 0.5-2 h for product B, and at 0.25-2.5 h for reference product. Bioequivalence (90 % CI lying within the acceptable range of 80.00-125.00 %) was met in 38 subjects receiving product A and 39 subjects receiving product B. Tramadol HCl/paracetamol FDTs were well tolerated. A total of 6 adverse events (AEs) were reported during the study (headache, giddiness, pain in abdomen, itching on forearms and thighs, and elevated eosinophil count), of which 3 were expected and possibly related to the study product. The AEs were mild to moderate in severity. No serious AE was observed during the study.  Discussion:  Data from the present study demonstrate the bioequivalence between Paxiflas(r) FDTs, administered with and without water in different periods, and tablets of Zaldiar(r), administered with water, in terms of rate and extent of absorption under fasting condition.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Bioequivalence]]></kwd>
<kwd lng="en"><![CDATA[tramadol]]></kwd>
<kwd lng="en"><![CDATA[paracetamol]]></kwd>
<kwd lng="en"><![CDATA[fast disintegrating tablets]]></kwd>
<kwd lng="en"><![CDATA[pain]]></kwd>
<kwd lng="en"><![CDATA[treatment]]></kwd>
<kwd lng="es"><![CDATA[Bioequivalencia]]></kwd>
<kwd lng="es"><![CDATA[tramadol]]></kwd>
<kwd lng="es"><![CDATA[paracetamol]]></kwd>
<kwd lng="es"><![CDATA[bucodispersable]]></kwd>
<kwd lng="es"><![CDATA[dolor]]></kwd>
<kwd lng="es"><![CDATA[tratamiento]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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