Interacción de los antineoplásicos orales con los alimentos: revisión sistemática

[email protected]ón: Los estudios de biodisponibilidad son parte integrante del desarrollo clínico de medicamentos para administración oral con el fin de identificar potenciales interacciones fármaco-alimento (iFA). Actualmente, para los antineoplásicos orales se empieza a reconocer su importancia clínica, aun cuando lamentablemente, la información disponible presenta variabilidad en su evidencia científica. Objetivos: Revisar la evidencia científica disponible sobre las interacciones de los alimentos con medicamentos antineoplásicos orales y establecer recomendaciones para su administración. Métodos: Se realizó una búsqueda bibliográfica en Medline y The Cochrane Library para el periodo comprendido entre enero de 1966 a marzo de 2008, enfocada a identificar las publicaciones sobre interacciones fármaco alimento con antineoplásicos orales. El análisis bibliográfico consta de dos fases. En la primera fase se excluyeron los artículos que por título y contenido del resumen no se correspondían con el objetivo planteado; en la segunda fase se eliminaron las referencias duplicadas en ambas bases de datos. Los criterios de inclusión para seleccionar los artículos fueron: diseño (revisiones sistemáticas, metaanálisis, ensayos clínicos randomizados Fase I y II), población (pacientes adultos; >19 años de edad), intervención evaluada (administración de antineoplásicos orales bajo condiciones de ayuno o con alimentos) y medida del resultado de la iFA (cálculo del IC90% de la razón entre la media geométrica de valores del área bajo la curva de concentraciones plasmáticas (ABC) o la concentración plasmática máxima (Cmax) con y sin alimentos). Se excluyeron las publicaciones que como medida de resultado no hacían referencia al dictamen de bioequivalencia establecido por la Food and Drugs Administration (FDA). La valoración crítica de los artículos seleccionados se realizó según las recomendaciones que de acuerdo con la FDA deben cumplir estos estudios. Resultados: En la búsqueda inicial se obtuvieron 850 referencias (98,5% Medline + y 1,4% Cochrane). En la primera fase se excluyeron el 87,7% (746) de los artículos, correspondiendo el 100% a la búsqueda en Medline. En la segunda fase, quedaron 40 artículos (5,2% de los iniciales) para su lectura crítica a texto completo, a los que se añadieron cuatro más no indexados en Medline. De la lectura crítica de los 44 artículos finales, se excluyeron 25 artículos (20 artículos originales, 4 comunicaciones cortas y 1 metanálisis) por no incluir como medida de resultado el dictamen de bioequivalencia. Los 19 (2,2%) artículos restantes proporcionaron información sobre 19 fármacos antineoplásicos orales, en 210 pacientes y 146 voluntarios sanos. De estos 19 fármacos, el 63% no presentan iFA o interacciones fármaco-alimento, pudiéndose administrar indistintamente con/sin alimentos; el 21% se deben administrar con alimentos y sólo el 16% presentan interacción fármaco alimento, por lo que se deben administrar sin alimentos. Discusión: Actualmente, la importancia clínica de las interacciones fármaco alimento con antineoplásicos orales se identifica más directamente con la seguridad del paciente que con la efectividad del tratamiento. Ante el desarrollo de estos agentes orales, su irrupción en la terapia oncológica desplazando a la terapia parenteral, con costes mensuales de miles de euros, hay necesidad de realizar estudios farmacocinéticos y farmacodinámicos bien diseñados. Su objetivo debe de ser comparar su biodisponibilidad en presencia o ausencia de alimentos con la respuesta clínica. Mientras tanto, establecer recomendaciones para su administración en relación con los alimentos, es inconsistente para algunos de estos fármacos y su resultado incierto por la falta de estudios fundamentados en el dictamen de bioequivalencia establecido por la FDA.Introduction: studies on bioavailability are part of the clinical development of drugs for oral use in order to identify potential drug-food interactions. For oral antitumor drugs, their clinical importance is currently recognized although regrettably the information available presents variability concerning the scientific evidence. Objectives: To review the available scientific evidence about oral anti-tumor medications and establish the recommendations for their administration with foods. Methods: We carried out a bibliographic search in Medline and The Cochrane Library for the period January of 1966 to March of 2008, focused on identifying those publications about drug-food interactions with oral antitumor medications. The bibliographical analysis was made in two steps. During the first phase, we excluded those articles in which the title or their content did not correspond with the objective settled; during the second phase, we deleted all the references duplicated in both databases. The inclusion criteria to select the articles were: design (systematic reviews, meta-analysis, Phase I and Phase II randomized clinical trials), population (adult patients; >19 years of age), intervention evaluated (administration of oral anti-tumor drugs under fasting conditions or with food) and measurement of the iFA results (calculation of the 90% CI of the odds ratio between the geometric mean of the values under the curve of the plasma concentrations (ABC) or the maximal plasma concentration (Cmax) with and without foods). We excluded those publications that did not make reference to the bioequivalence dictamen established by the Food and Drugs Administration (FDA) in their outcomes measurement. A critical appraisal of the selected articles was done according to the recommendations that the FDA established to be met by these studies. Results: At the initial search we obtained 850 references (98.5% Medline + and 1.4% Cochrane). During the first phase, we excluded 87.7% (746) of the articles, 100% of them corresponding to the search in Medline. During the second phase, 40 studies remained (5.2% of the initial ones) for full-text critical appraisal, to which four studies were added not indexed in Medline. From the critical appraisal of the 44 final articles, 25 were excluded (20 original articles, 4 short communications, and 1 meta-analysis) because they did not include as an outcome measure the bioequivalence dictamen. The 19 (2.2%) remaining articles provided information on 19 oral anti-tumor drugs in 210 patients and 146 healthy volunteers. Of these 19 drugs, 63% did not present drugfood interactions, with the possibility of administering them either with or without food; 21% have to be administered with foods and only 16% present drug-food interactions, so they have to be administered without foods. Discussion: Currently, the clinical importance of drugfood interactions with oral anti-tumor drugs is identified more directly with the patient's safety than with the efficacy of the therapy. Given the development of these oral agents, their incorporation into the oncologic strategy displacing parenteral therapy, with monthly costs of thousands of Euros, it is necessary to perform well-designed studies on pharmacokinetics and pharmacodynamics. Their goal has to be comparing their bioavailability in the presence or absence of foods with the clinical response. In the meanwhile, to establish recommendations for their administration in relation to foods is inconsistent for some of these drugs and their results is uncertain given the lack of studies based on the FDAbioequivalence dictamen

Optical spectroscopy of 4U 1812-12: an ultra-compact X-ray binary seen through an H II region

The persistent, low-luminosity neutron star X-ray binary 4U 1812-12 is a potential member of the scarce family of ultra-compact systems. We performed deep photometric and spectroscopic optical observations with the 10.4 m Gran Telescopio Canarias in order to investigate the chemical composition of the accreted plasma, which is a proxy for the donor star class. We detect a faint optical counterpart (g~25, r~23) that is located in the background of the outskirts of the Sharpless 54 H II region, whose characteristic nebular lines superimpose on the X-ray binary spectrum. Once this is corrected for, the actual source spectrum lacks hydrogen spectral features. In particular, the Halpha emission line is not detected, with an upper limit (3 sigma) on the equivalent width of <1.3 A. Helium (He I) lines are neither observed, albeit our constraints are not restrictive enough to properly test the presence of this element. We also provide stringent upper limits on the presence of emission lines from other elements, such as C and O, which are typically found in ultra-compact systems with C-O white dwarfs donors. The absence of hydrogen features, the persistent nature of the source at low luminosity, as well as the low optical to X-ray flux ratio confirm 4U 1812-12 as a compelling ultra-compact X-ray binary candidate, for which we tentatively propose a He-rich donor based on the optical spectrum and the detection of short thermonuclear X-ray bursts. In this framework, we discuss the possible orbital period of the system according to disc instability and evolutionary models.Comment: Accepted for publication in A&

α-Glucosidase and α- amylase inhibition potentials of ten wild Mexican species of Verbenaceae

Purpose: To evaluate the inhibitory activity of 10 wild Verbenaceae species from Mexico against α- glucosidase and α-amylase.Methods: Ethanol leaf extracts of 10 Verbenaceae species from Mexico were prepared. The inhibitory activity of the extracts against α-glucosidase and α-amylase was evaluated using enzymatic protocols. At least four serial diluted concentrations of each extract was used to calculate the half-maximal inhibitory concentration (IC50).Results: The 10 evaluated Verbenaceae species showed high α-glucosidase inhibition activity, but a low inhibitory effect on α-amylase. Aloysia gratissima (IC50 = 0.122 mg/mL), Verbena carolina (IC50 = 0.112 mg/mL), Bouchea prismatica (IC50 = 0.122 mg/mL), Verbena menthiflora (IC50 = 0.071mg/mL) and Priva mexicana (IC50 = 0.032 mg/mL) exhibited the strongest inhibitory activities against α- glucosidase.Conclusion: All the Verbenaceae species studied possess α-glucosidase inhibitory effect, with P. mexicana being the one with the strongest activity. These findings demonstrate the highs potential of these species as a source of natural antihyperglycemic agents for type 2 diabetes therapy.Keywords: Hyperglycemic, Diabetes, α-Glucosidase, α-Amylase Verbenaceae, Aloysia gratissima, Bouchea prismatica, Priva mexican

The Spatial Distribution of Complex Organic Molecules in the L1544 Pre-stellar Core.

journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05journal_title: The Astrophysical Journal article_type: paper article_title: THE SPATIAL DISTRIBUTION OF COMPLEX ORGANIC MOLECULES IN THE L1544 PRE-STELLAR CORE copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2016-05-27 date_accepted: 2016-09-12 date_epub: 2016-10-05The detection of complex organic molecules (COMs) toward cold sources such as pre-stellar cores (with T<10 K), has challenged our understanding of the formation processes of COMs in the interstellar medium. Recent modelling on COM chemistry at low temperatures has provided new insight into these processes predicting that COM formation depends strongly on parameters such as visual extinction and the level of CO freeze out. We report deep observations of COMs toward two positions in the L1544 pre-stellar core: the dense, highly-extinguished continuum peak with A V ≥30 mag within the inner 2700 au; and a low-density shell with average A V ~7.5-8 mag located at 4000 au from the core's center and bright in CH3OH. Our observations show that CH3O, CH3OCH3 and CH3CHO are more abundant (by factors ~2-10) toward the low-density shell than toward the continuum peak. Other COMs such as CH3OCHO, c-C3H2O, HCCCHO, CH2CHCN and HCCNC show slight enhancements (by factors ≤3) but the associated uncertainties are large. This suggests that COMs are actively formed and already present in the low-density shells of pre-stellar cores. The modelling of the chemistry of O-bearing COMs in L1544 indicates that these species are enhanced in this shell because i) CO starts freezing out onto dust grains driving an active surface chemistry; ii) the visual extinction is sufficiently high to prevent the UV photo-dissociation of COMs by the external interstellar radiation field; and iii) the density is still moderate to prevent severe depletion of COMs onto grains

A MIMO-OFDM testbed, channel measurements, and system considerations for outdoor-indoor WiMAX

The design, implementation, and test of a real-time flexible 2×2 (Multiple Input Multiple Output-Orthogonal Frequency Division Multiplexing) MIMO-OFDM IEEE 802.16 prototype are presented. For the design, a channel measurement campaign on the 3.5GHz band has been carried out, focusing on outdoor-indoor scenarios. The analysis of measured channels showed that higher capacity can be achieved in case of obstructed scenarios and that (Channel Distribution Information at the Transmitter) CDIT capacity is close to (Channel State Information at the Transmitter) CSIT with much lower complexity and requirements in terms of channel estimation and feedback. The baseband prototype used an (Field Programmable Gate Array) FPGA where enhanced signal processing algorithms are implemented in order to improve system performance. We have shown that for MIMO-OFDM systems, extra signal processing such as enhanced joint channel and frequency offset estimation is needed to obtain a good performance and approach in practice the theoretical capacity improvements

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at &#8730;s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|&#60;2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions