Medicamentos bioterapéuticos: uso de toxinas botulínicas en la era de biosimilares / Biotherapeutic medicines: use of botulinum toxins in the era of biosimilars

Introducción: Las toxinas botulínicas son medicamentos bioterapéuticos con grandes aplicaciones en el campo de la neurología, como la cefalea y los movimientos anormales. Debido a la importancia médica y al incremento de las indicaciones terapéuticas de la toxina botulínica, este artículo pretende hacer claridad acerca de la terminología básica con respecto a la naturaleza de este medicamento, a las diferencias estructurales con medicamentos convencionales y aspectos importantes en relación con su potencia biológica e inmunogenicidad, para así comprender las potenciales diferencias entre las toxinas disponibles y conceptuar en torno a la no intercambiabilidad o sustitución de una toxina por otra. Materiales y métodos: Revisión no sistemática, según lo recomendado en la Escala para la Verificación de los Artículos Revisiones Narrativas (Sanra). Conclusiones: Los medicamentos biológicos no son intercambiables entre sí, aunque demuestren bioequivalencia. No se pueden evaluar como medicamentos genéricos intercambiables porque son biológicos; no existen estudios comparativos cabeza a cabeza; son diferentes, debido al proceso individual de manufactura.

Introduction: Botulinum toxins are biotherapeutic drugs with great applications in the field of neurology such as headache and abnormal movements. Due to the medical importance and the increase in therapeutic indications of botulinum toxin, this article aims to clarify the basic terminology regarding the nature of this drug, the structural differences with conventional drugs and important aspects in relation to its biological potency and immunogenicity in order to understand the potential differences between the available toxins and conceptualize regarding the non-interchangeability or substitution of one toxin for another. Materials and methods: Non-systematic review as recommended in the Scale for the Verification of Narrative Review Articles (SANRA). Conclusions: Biological drugs are not interchangeable with each other, even if they demonstrate bioequi-valence. They cannot be evaluated as interchangeable generic drugs because they are biologics. There are no head-to-head comparative studies. They are different due to the individual manufacturing process.

Unani concept of drug substitution (therapeutic interchange) and its validation on scientific parameters

Background: Unani concept of therapeutic interchange, despite having immense practical aspect, has notbeen touched upon in a coherent way by most of the Unani scholars except Razi (Rhazes 865e925 AD),who took the concept plausibly and framed rules for alternate drug prescription at the time ofunavailability of the drugs of choice.Objective: The Unani concept of therapeutic interchange is based on similarity in action, temperamentand physical properties of drugs mainly botanicals, which are already established and need no furtherdiscussion; however, phytochemistry has not been considered a basis for substitution. Therefore,objective of this study was evaluation of the concept on phytochemical parameters as actions of mostdrugs are due to phytoconstituents.Material and methods: Classical Unani literature pertaining to therapeutic interchange and ethnobotanical literature for uses and phytoconstituents of three botanicals and their respective substitutes werereviewed. Ethnobotanical literature was collected from well known search engine viz., PubMed, GoogleScholar, Scopus and Science direct. In view of exploring the concept on scientific basis, physicochemical,phytochemical and analytical (HPLC, GCeMS) studies were also conducted.Results: The study exhibited similarity in phytoconstituents in main and substitute botanicals withinsignificant differences. Direct relation between doses, actions, intensity of actions, temperament andchemical constituents of main and substitute botanicals was observed.Conclusion: The study, however, seemed to validate the concept on the basis of phytoconstituents, furtherpharmacological studies on the basis of properties and activities is required to strengthen the concept

Therapeutic Interchange: New Initiative System in Saudi Arabia

Objective: To validate the therapeutic interchange system at healthcare institutions as new initiatives in the Kingdom of Saudi Arabia. Methods: It is a new initiative project drove by national therapeutic interchange system programs. The projects drove the therapeutic interchange system guidelines and the international business model, pharmacy project guidelines project management institution guidelines of a new project. The initiative project is written through project management professionals and contained of several parts, including the initial phase, the planning phase, the execution phase and the monitoring and controlling phase. Results: The therapeutic interchange services with a defined vision, mission and goals. The services had various aids, including clinical and economical, on patients and the healthcare system, as exemplified in the assessment. The continuation was of the project assured by the risk management model description. Besides, the monitoring and controlling of the services as declared. The transition to operation project, though closing the project stage, explored in the analysis. Conclusion: The therapeutic interchange system is a new initiative, part of the formulary management. There are various therapeutic interchange system classes of medications can be started though antibiotics, gastrointestinal medications and anti-psychiatric medications; it is highly recommended to implement in Saudi Arabia.

Application of ADaM in safety analysis of bioequivalence trail of generic drugs / 中国临床药理学与治疗学

AIM: To promote the Clinical Data Inter-change Standards Consortium (CDISC) standard in clinical trials and promote the standardization of clinical trial data. METHODS: To combine the implementation guide of Analysis Data Model (ADaM) and common problems of actual data, and to introduce the application of analytical data model ADaM in the safety of bioequivalence trails of generic drugs. RESULTS: For different types of clinical trial data, according to various situations that may occur, a safety analysis data set that meets the standards was generated. CONCLUSION: Under the background of the continuous development of generic drugs in China and the low degree of standardization of clinical trial data, the use of CDISC standards in clinical research can promote the standardization of clinical trial data, and can also shorten the time of statistical analysis and accelerate the process of drug development.

Intercambialidade de produtos biológicos no Sistema Único de Saúde (SUS): principais desafios regulatórios / Interchangeability of biological products in the Brazilian Unified National Health System (SUS): the main regulatory challenges / Intercambiabilidad de productos biológicos en el Sistema Único de Salud (SUS): principales desafíos regulatorios

Resumo: Produtos biológicos revolucionaram a terapêutica mundial. O alto custo desses medicamentos, no entanto, ameaça a sustentabilidade dos sistemas de saúde. O desenvolvimento de cópias é tido como uma alternativa econômica, mas devido à complexidade desses produtos, muitos conceitos utilizados para os medicamentos genéricos não se aplicam. A intercambialidade entre produtos biológicos representa um desafio regulatório a ser superado. Este ensaio discute os principais desafios regulatórios relacionados ao estabelecimento de critérios para intercambialidade entre produtos biológicos novos e suas cópias no âmbito do Sistema Único de Saúde (SUS), considerando as diretrizes adotadas pelas principais agências reguladoras de medicamentos do mundo sobre a intercambialidade e o arcabouço regulatório vigente no Brasil para esta questão. Preocupações relacionadas à intercambialidade de produtos biológicos incluem substituição automática, nomenclatura, farmacovigilância, imunogenicidade e extrapolação das indicações terapêuticas e dos dados clínicos de produtos biológicos novos para suas cópias. Embora o sucesso clínico e os benefícios econômicos da alternância entre alguns produtos biológicos novos e seus biossimilares já tenham sido observados, a heterogeneidade das barreiras regulatórias para aprovação das cópias de produtos biológicos entre diferentes países deve ser considerada para a regulamentação da intercambialidade de produtos biológicos no Brasil.

Abstract: Biological products have sparked a worldwide therapeutic revolution. However, the high cost of these products threatens health systems' sustainability. The development of copies is considered an economic alternative, but due to the products' complexity, many concepts used in generic drugs do not apply. Interchangeability between biologicals poses a regulatory challenge. This essay discusses the main regulatory challenges for establishing criteria for interchangeability between new biologicals and their copies in the scope of the Brazilian Unified National Health System (SUS), considering the guidelines adopted by the world's main drug regulatory agencies concerning interchangeability and the prevailing Brazilian regulatory framework on this issue. Concerns related to the interchangeability of biologicals include automatic substitution, nomenclature, pharmacovigilance, immunogenicity, and extrapolation of therapeutic indications and clinical data from new biologicals to their copies. While the clinical success and economic benefits of switching from new biologicals to their biosimilars have already been observed, the heterogeneity between countries in the regulatory barriers to the approval of copies of biologicals should be taken into consideration during the regulation of interchangeability of biologicals in Brazil.

Resumen: Los productos biológicos revolucionaron la terapéutica mundial. El alto coste de estos medicamentos, no obstante, amenaza la sostenibilidad de los sistemas de salud. El desarrollo de copias se considera como una alternativa económica, pero debido a la complejidad de estos productos, muchos conceptos utilizados para los medicamentos genéricos no se aplican a los mismos. La intercambiabilidad entre productos biológicos representa un desafío regulatorio que se debe superar. Este trabajo discute los principales desafíos regulatorios, relacionados con el establecimiento de criterios para la intercambiabilidad entre productos biológicos nuevos y sus copias en el ámbito del Sistema Único de Salud (SUS), considerando las directrices adoptadas por las principales agencias regulatorias de medicamentos del mundo sobre la intercambiabilidad y el armazón regulatorio vigente en Brasil para esta cuestión. Las preocupaciones relacionadas con la intercambiabilidad de productos biológicos incluyen la sustitución automática, nomenclatura, farmacovigilancia, inmunogenicidad y extrapolación de las indicaciones terapéuticas, así como de los datos clínicos de productos biológicos nuevos para sus copias. A pesar de que el éxito clínico y los beneficios económicos de la alternancia entre algunos productos biológicos nuevos y sus biosimilares, ya se han observados, la heterogeneidad de las barreras regulatorias para la aprobación de las copias de productos biológicos entre los diferentes países debe ser considerada para la regulación de la intercambiabilidad de productos biológicos en Brasil.

Evaluación de la intercambiabilidad in vitro de diferentes marcas de tabletas de diclofenaco sódico disponibles en el mercado colombiano / In vitro evaluation of the interchangeability of different brands of diclofenac sodium tablets available in the Colombian market

Introducción. El diclofenaco sódico se clasifica como un antiinflamatorio no esteroide. Dado que es de venta libre, el paciente no tiene ningún seguimiento por parte de los equipos de salud, y como sus fuentes son múltiples, es necesario establecer la equivalencia entre ellas en estudios in vitro, que son los más prácticos y plantean un menor compromiso ético. Objetivos. Determinar la intercambiabilidad de diferentes marcas comerciales de diclofenaco sódico comparadas con el producto innovador mediante un estudio in vitro de tabletas comerciales de 50 mg, según los lineamientos del Sistema de Clasificación Biofarmacéutica (SCB). Materiales y métodos. Se desarrollaron pruebas físicas y químicas siguiendo las indicaciones de laedición 39 de la United States Pharmacopeia (USP). Para la cuantificación, se validó una metodología analítica según lo establecido en la mencionada farmacopea y la guía Q2 del International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Los perfiles de disolución y sus análisis se rigieron por lo establecido por la Organización Mundial de la Salud y las normas nacionales. Resultados. Todos los productos aprobaron las pruebas físicas. En cuanto a la disolución, la etapa ácida también fue superada por todas las marcas, pero una marca falló en la etapa alcalina. El análisis de similitud reveló que solo un producto fue equivalente al innovador y tres fueron supradisponibles, aunque dichas marcas también podrían considerarse equivalentes al producto innovador. Conclusiones. De las ocho marcas evaluadas, tres no cumplieron totalmente con la prueba de valoración del principio activo y del porcentaje de disolución; solo una marca fue intercambiable con el producto innovador y tres fueron supradisponibles comparadas con este, por lo cual no constituyen un riesgo para el paciente.

Introduction: Diclofenac sodium is classified as a non-steroidal anti-inflammatory drug. As diclofenac is an over-the-counter drug, its use among patients cannot be monitored by health teams in follow-up sessions. Given the multiple sources of diclofenac sodium, their interchangeability must be investigated, particularly in the form of in vitro studies, which are the most practical research type and entail minimal ethical commitment. Objectives: To determine the interchangeability of the different commercial brands of diclofenac sodium relative to the innovative product, this work carries out an in vitro study of eight commercial products of diclofenac sodium (50 mg) following the guidelines of the Biopharmaceutical Classification System. Materials and methods: Physical and chemical tests were developed following the guidelines of the 39th edition of the United States Pharmacopoeia. An analytical methodology was validated for the quantification of diclofenac according to the current pharmacopoeia and the Q2 guideline ofthe International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). Dissolution profiles and their analyseswere governed by the regulations established by the World Health Organization and the national regulations. Results: All the products passed the physical tests. In the dissolution assays, the acid stage was overcome by all brands, but in the alkaline stage, one brand failed. The analysis of the similarities revealed that only one product was equivalent to the innovator and that three were supra-available, although these brands could also be considered equivalent to the innovator. Conclusions: Of the eight brands evaluated, three failed the test forthe active principle and the percentage of dissolution. Only one brand was found to be interchangeable with the innovator, and three were identified to besupra-availableand, thus, they do not present a risk for patients.

Experiencia Programa de Intercambio Residentes Neuropediatría Chile-Hospital de Niños de Boston / Interchange Program Experience Pediatric Neurology Residents of Chile-Boston Children's Hospital

Cada dos años, residentes de Neuropediatría de distintos centros en Chile visitan el Boston Children's Hospital a fin de dar vida a un intercambio académico bilateral, que se constituye como una valiosa instancia de aprendizaje bilateral. Pensamos que es importante relatar nuestra experiencia y al mismo tiempo hacer algunas reflexiones sobre esta instancia formativa. Palabras Claves: Residentes; Intercambio; Neuropediatría; Educación médica

Every two year, residents of pediatric neurology from different Chilean Universities visit the Boston Children's Hospital for a bilateral academic exchange, that constitutes a valuable learning instance. We think that it is important to relate our experience and share our thoughts about this interchange. Key words: Residents; Interchange; Pediatric Neurology; Medical Education.

Application of Clinical Data Interchange Standards Consortium (CDISC) Standards to Electronic Data Capture System / 世界科学技术-中医药现代化

Data acquisition is one of the key links that influencing the quality of clinical research.Electronic data capture system (EDC) embodies the advantages of saving time,manpower and material resources and improving efficiency and reliability by data acquisition.CDISC has established worldwide industry standards to support the electronic acquisition,exchange,submission and archiving of clinical research data.The application of CDISC standards to EDC system is favorable in ensuring the validity and standardization of clinical data.This paper takes the Oracle's OC/ RDC (Oracle Clinical / Oracle Remote Data Capture) system as an example to discuss the application of CDISC standard to EDC system from the two aspects:direct application and indirect application.We suggest that data collection should be taken into account during the design phase of a clinical trial,and the CDISC standard be applied at the CRF design stage.A design for eCRF takes time and effort by the combination of EDC system and CDISC standard,while thoughtless design may collect the wrong data.Therefore,it is suggested that a specialized personnel should be put in charge of eCRF design and maintenance during the operation of EDC system,and a set of standardized eCRFs based on CDISC standard and standard operating procedures should be built in one organization.

Exploration on Internal and External Network Security Construction of Hospitals in the New Era / 医学信息学杂志

On the basis of summarizing the general situation of current internal and external network construction of hospitals,the paper introduces the main hidden dangers of hospital network security,puts forward internal and external network security management measures,and elaborates the internal and external network security construction principle,network topology structure,and network construction achievements of the First Affiliated Hospital of Guangxi Medical University.

A Preliminary Discussion of Application of CDISC Standards in Clinical Research Data Management of New Traditional Chinese Medicine / 中国中医药信息杂志

In this article, a new TCM clinical trial of phaseⅢ was served as an example of application of Clinical Data Interchange Standards Consortium (CDISC). It briefly introduced seven data acquisition modules commonly used in clinical research of new traditional Chinese medicine, namely demographics, subject characteristic, clinical event, medical history, questionnaire, laboratory inspection and adverse event. It also introduced the process of transferring the above modules to Study Data Tabulation Models (STDM), and discussed the feasibility and some issues that required attention of CDISC application in clinical research of new traditional Chinese medicine.

Condiloma acuminado y embarazo. Consideraciones en la atención prenatal / Condyloma Acuminatum and pregnancy. Considerations of the prenatal attention

Fundamento: El condiloma acuminata prevalece en la población mundial elevando su incidencia en los últimos años; afectando proporcionalmente a la población gestante. Un número elevado de embarazadas son sometidas a la operación cesárea por esta causa, elevando los riesgos de morbimortalidad perinatal. El conocimiento del modo de trasmisión durante el embarazo, las consecuencias para la descendencia y la conducta a seguir ante las verrugas genitales durante la gestación, pueden contribuir a modificar el manejo de esta enfermedad durante la atención prenatal. Objetivo: Analizar algunas evidencias necesarias para un adecuado seguimiento prenatal en las gestantes que padecen de condiloma verrucoso genital. Desarrollo: Se realizó una revisión bibliográfica exhaustiva y actualizada acerca de las vías de trasmisión de la madre al hijo y la conducta obstétrica en las gestantes afectadas por condilomas acuminados. Conclusiones: Las evidencias científicas que se sintetizan en la revisión nos muestran que la condilomatosis genital durante el embarazo puede ser trasmitida de la madre al hijo por diferentes vías; no evitando la cesárea electiva la infección viral al recién nacido. Diversos tratamientos aplicados de forma adecuada durante la atención prenatal pueden disminuir este riesgo.

Background: The Condyloma acuminatun prevails in the world population increasing its incidence in the last few years and affecting proportionally to the population in the gestation period. A high number of pregnant women are submissive to a caesarean operation for this cause, increasing the risk of perinatal morbimortality. The knowledge of the way of transmission during the pregnancy, the consequences for the descent and the conduct to follow in the presence of genitals wart during the gestation, can contribute to modify the management of this disease during the prenatal attention. Objective: Analyze some evidences needed for an adequate prenatal pursuit in women that suffer condyloma acuminatum in the gestation period. Development: An exhausted and actual bibliography study was done about the way of transmission from the mother to her child and the obstetric conduct in women in the gestation period affected by the condyloma acuminatum. Conclusions: The scientific evidence summarized in the study showed us that genital condylomatosis during pregnancy can be transmitted from the mother to her child by different ways, not only avoiding the elected caesarean operation the viral infection to the newborn. Different treatments applied correctly during the prenatal attention can decrease this risk.

Avaliação da qualidade e equivalência farmacêutica de comprimidos contendo 10mg de sinvastatina / Assessment of quality and pharmaceutical equivalence of 10 mg simvastatin tablets

A sinvastatina, pertencente à classe das estatinas, é um importante fármaco redutor do colesterol e é encontrada comercialmente como medicamentos referência, genéricos e similares em diferentes dosagens, sendo a de 10 mg a mais comum. Este trabalho tem como objetivo avaliar a qualidade e a equivalência entre comprimidos de sinvastatina 10 mg comercializados no mercado brasileiro. Foram selecionados dois medicamentos similares, um genérico e referência. Os ensaios de controle de qualidade aplicados foram: determinação do peso médio, dureza, friabilidade, desintegração, teor de princípio ativo, uniformidade de conteúdo e dissolução in vitro. Para tanto, foi necessário desenvolvimento e validação de metodologia por espectrofotometria na região do ultravioleta (UV). As formulações apresentaram-se dentro dos limites preconizados para todas as análises. No entanto, quando analisou-se estatisticamente os perfis de dissolução, verificou-se a não equivalência entre os medicamentos similares e o de referência. Porém, através dos resultados obtidos, podemos evidenciar a equivalência entre o genérico e o de referência, sugerindo sua intercambialidade...

Simvastatin, a well-known medicine of the statin class, is used therapeutically for the reduction of cholesterol and is commercially available in reference, similar and generic forms, in various doses, the tablet of 10 mg being the commonest in prescriptions. The purpose of this study was to test the quality and the pharmaceutical equivalence of tablets containing 10 mg of simvastatin available on the Brazilian market. One generic, one reference and two similar dosage forms were selected. The quality-control variables used were: weight variation, hardness, friability, disintegration, content of the active principle, content uniformity and dissolution in vitro. A UV-spectrophotometric method was developed and validated. All formulations were approved in the quality analysis. By using mathematical and statistical models, it was observed that the dissolution profiles of the similar dosage forms were not equivalent to that of the reference. On the other hand, when the generic medicine was compared with the reference, their interchangeability was confirmed...

<b>Expectations and Challenges Regarding the Use of the SS-MIX in a Clinical Trial </b> / 薬剤疫学

While there is an advantage to be able to directly utilize some research database of medical information must solve several problems. It also includes support for international standardization, led by computerized system validation, and CDISC. We should countermeasures with epidemiological studies using SS-MIX standardized storage, in anticipation of its application to clinical trials in the near future in Japan. (Jpn J Pharmacoepidemiol 2013；18(1)：35-39)

Se deixando levar pelas Passagens / Allowing oneself to be taken by the Passages / Dejándose llevar por los Pasajes

O metabolizado foi um ponto em destaque da entrevista. Daí foram surgindo ideias em mim quanto a troca emocional, afetiva no encontro com corpos - experiências que trazem um acréscimo ao ser, abrindo passagens para a circulação de mais vida, em um movimento como o de escrever: ponto de partida de novas metabolizações, novas passagens.

The metabolized was a point in evidence of the interview, from which ideas materialized in me relating to the emotional and affective interchange in the encounter with bodies - experiences which add to the being, opening passages for the circulation of more life in a movement such as writing a starting point of new metabolisms, new passages.

Lo metabolizado fue un punto destacado en la entrevista y a partir de ahí me fueron surgiendo ideas al respecto del intercambio emocional, afectivo en el encuentro con cuerpos - experiencias que traen un complemento al ser, abriendo pasajes para la circulación de más vida en un movimiento como el de escribir un punto de partida de nuevas metabolizaciones, nuevos pasajes.

Equidad en intercambios de esfuerzo y ganancias: efectos de la información / Equity in Effort and Profits Interchanges: Effects of Information

Este trabajo aborda experimentalmente el estudio de los intercambios equitativos en una tarea en la que doce díadas de estudiantes de licenciatura en psicología asignaban a su compañero uno de tres posibles "juegos" asociados con requisitos diferenciales de un programa de reforzamiento de razón variable (RV: 5, 10 o 20). En una segunda condición, los participantes asignaban también la cantidad de puntos que obtendría su pareja (1, 2 o 4 puntos) con cada requisito de razón. Se programaron dos clases de sesiones: con información o sin información de la asignación de juego que hacían los compañeros en cada ensayo. Para evaluar las estrategias utilizadas se empleó el modelo Aristotélico de la Equidad (Adams, 1965; Anderson, 1976), mismo que describió adecuadamente la razón de esfuerzo y ganancias en los intercambios bajo la condición de información. Se discuten aquellas estrategias diádicas que resultaron en una distribución de mayor cantidad de ganancias con el menor esfuerzo posible, así como aquellas que produjeron distribuciones asimétricas de ganancias y esfuerzo, lo que desencadenó ganancias relativamente reducidas a lo largo de las sesiones. Especial énfasis recibe la discusión del mecanismo de reciprocidad en el intercambio social.

This paper deals with the experimental study of equitable interchanges in a task where 12 dyads of psychology students assigned their partners one of three games associated with different values of a variable ratio schedule of reinforcement (VR: 5, 10 or 20). In a second condition, subjects also assigned the number of points (1, 2 or 4 points) that their partners could obtain after completing the VR response criteria. Two types of sessions were programmed in which the information about task allocation and point's assignment was either present or absent. The Aristotelic model of Equity was used (Adams, 1965; Anderson, 1976) to evaluate the interchange strategies, and to describe the ratio of effort and profits in the interchanges under the information condition. The patterns of dyadic strategies that maximized profits and minimized effort were analyzed. The reciprocity mechanism in social interchange is discussed.

Comparación de la biodisponibilidad y la farmacocinética entre dos formulaciones de tabletas de metforminade 850 mg en voluntarios colombianos sanos / Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers

Purpose: The aim of this study was to compare the bioavailability of two formulations of metformin 850 mg tablets: Glucophage® from Merck Santè laboratories (reference product) and Metformin from Winthrop Pharmaceuticals de Colombia SA (test product) in healthy Colombian volunteers.Methods: A random, double blind, two-period, two-week wash out period, crossover study was performed in 24 healthy male and female volunteers for a single 850-mg dose of metformin tablets administrated with 240 ml of water after 12 hours of fasting. Once the drug was administrated, blood samples were collected before and within 24 hour, and plasma metformin concentration was determined by using a validated HPLC method. Pharmacokinetic parameters such as Cmax, AUC0-96h, AUC0-∞, and Tmax were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed Cmax and AUC0-∞ values were within the equivalence range of 80%-125%.Results: ANOVA analysis of the ln-transformed Cmax and AUC0-∞ indicated that none of the effects examined (formulation, period, within and between-subjet variances and carry over) was statistically significant. The mean (±SD) of Cmax 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and Tmax 2.57 (± 0.93) h vs. 2.22 (± 0.94) h were obtained with test and reference formulations, respectively. These pharmacokinetic parameters presented differences with the results from other published papers. The 90% confidence interval of the logarithmic ratio of AUC0-∞ and Cmax was within the range of 80-125%.Conclusions: In this study in healthy Colombian volunteers, a single 850-mg dose of metformin tablet test formulation met the criteria for bioequivalence to the reference formulation based on pharmacokinetic parameters AUC0-∞ and Cmax.

Objetivo: El objetivo de este estudio es comparar la bioequivalencia de dos formulaciones de tabletas de metformina de 850 mg: Glucophage® del Laboratorio Merck Santè (producto de referencia) y metformina de Laboratorios Winthrop Pharmaceuticals de Colombia SA (producto de prueba), en voluntarios colombianos sanos.Métodos: Se realizó un estudio aleatorizado, doble ciego, cruzado, en dos períodos y con un tiempo de lavado de dos semanas, en 24 voluntarios sanos, hombres y mujeres, que recibieron una dosis única de metformina de 850 mg, con 240 ml de agua, después de 12 horas de ayuno. Luego de la administración del medicamento, se recolectaron muestras de sangre durante 24 horas y las concentraciones plasmáticas de metformina se determinaron con un método de HPLC validado. Se calcularon los parámetros farmacocinéticos: Cmax, AUC0-96h, AUC0-∞, y Tmax. Las formulaciones se consideraron bioequivalentes si la relación de la media transformada a ln de Cmax y AUC0-∞ estaba dentro del rango de bioequivalencia de 80% a 125%.Resultados: El Anova de los datos transformados a ln de Cmax y AUC0-∞ indicaron que ninguno de los efectos analizados (formulación, período, variación intra e intersujetos y arrastre) fueron estadísticamente significativos. La media (±SD) de los parámetros obtenidos para los productos de prueba y de referencia, respectivamente, fueron: Cmax 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and Tmax 2.57 (± 0.93) h vs. 2.22 (± 0.94) h. El intervalo de confianza de la relación logarítmica del AUC0∞ y Cmax se encontró dentro del rango de 80% a 125%.

Metanálise de estudos de bioequivalência: a intercambiabilidade de genéricos e similares que contêm hidroclorotiazida é possível, mas não àqueles com maleato de enalapril / Meta-analysis for bioequivalence studies: interchangeability of generic drugs and similar containing hydrochlorothiazide is possible but not with enalapril maleate

INTRODUÇÃO: O programa de genéricos no Brasil propiciou maior acesso da população a medicamentos. Para garantir a intercambiabilidade entre medicamentos referência e genérico ou similar, é necessário que eles sejam bioequivalentes. Com o crescimento do número de medicamentos genéricos, é comum que pacientes o substituam por outro genérico ou similar. Contudo, essa troca pode não garantir a manutenção da bioequivalência. Para avaliar a segurança na intercambiabilidade entre diferentes genéricos e similares com hidroclorotiazida e maleato de enalapril, foi realizada metanálise de vários estudos de bioequivalência que utilizaram esses medicamentos. MÉTODOS: Foram utilizados dados provenientes de estudos de bioequivalência de genéricos e similares registrados pela Agência Nacional de Vigilância Sanitária (Anvisa). A compatibilidade dos dados de cada um dos estudos foi analisada, e a determinação de um intervalo de confiança para as diferenças entre as médias dos parâmetros farmacocinéticos, área sob a curva (ASC) e concentração plasmática máxima (Cmáx ), foi feita para cada estudo por meio da metanálise. RESULTADOS: A intercambiabilidade entre as combinações dos três produtos com Hidroclorotiazida foi confirmada com base nos intervalos de confiança obtidos. Para os medicamentos com maleato de enalapril, a intercambiabilidade não foi confirmada em 50 por cento das comparações estudadas dos produtos. CONCLUSÃO: A intercambiabilidade foi comprovada entre os três produtos com hidroclorotiazida. No entanto, para o maleato de enalapril, metade dos produtos estudados não é intercambiável, uma vez que não contempla os intervalos preconizados pelos testes de bioequivalência; portanto, a resposta farmacocinética e, por conseguinte, a efetividade do medicamento podem ser alteradas.

INTRODUCTION: The generic drugs program provided a better population's access to medicines. To ensure interchangeability between a brand-name and generic or similar drugs is necessary that they are bioequivalent. With the growing number of generic drugs, it is common for patients to replace a generic to another or one similar. However, this exchange can not guarantee the maintenance of bioequivalence. To evaluate the safety interchangeability between different generic and similar drugs with hydrochlorothiazide and enalapril maleate, a meta-analysis was carried out with several bioequivalence studies with these drugs. METHODS: Data from bioequivalence of generic and similar drugs approved by the National Health Surveillance Agency (Anvisa) (drug regulatory agency in Brazil) were used. The compatibility of data from each study was analyzed and the determination of a confidence interval for the differences between the means of pharmacokinetic parameters, area under the curve (ASC0-t) and maximum plasma concentration (Cmax), was made for each study by meta-analysis. RESULTS: The interchangeability between the combinations of the three products with hydrochlorothiazide was confirmed based on the obtained confidence intervals. For the drugs studied with enalapril maleate interchangeability has not been confirmed for 50 percent of the product comparisons. CONCLUSION: The exchange was established between the three products with hydrochlorothiazide. However, for the enalapril maleate half of the products studied are not interchangeable, considering they do not match the established intervals for bioequivalence tests, so the pharmacokinetics behavior and thus the effectiveness of the product may be changed.

Survey Results of Medical Insurance Reimbursement System for Independent Medical Laboratories in Korea / 대한진단검사의학회지

BACKGROUND: A questionnaire survey was performed to perceive the problem of the current medical insurance reimbursement system for laboratory tests referred to independent medical laboratories; then, we intended to find a way to improve the reimbursement system. METHODS: Questionnaires were distributed to 220 independent medical laboratories and 700 laboratory physicians from July through October 2005. Frequency analysis was used to analyse the replies from 109 respondents to 25 questionnaire items regarding the current medical insurance reimbursement system for referral tests, problems with the system, and suggestions for the improvement of the system. RESULTS: Among the 109 respondents to this survey, 49 (45.8%) considered the current reimbursement system to be unsatisfactory, while only 16 (15.0%) answered satisfactory. The problem was that the referral clinics-not the laboratories that performed the tests--would first receive their reimbursement for the laboratory tests from Health Insurance Review Agency (HIRA) and then give a portion of the laboratory test fees to the independent medical laboratories after the deduction of administrative fees. They (62.5% of the respondents) would prefer a separated reimbursement system by which the referral clinic-as well as the independent medical laboratory-would receive their reimbursement directly from HIRA through an Electronic Data Interchange (EDI) system. In this new system, 34% of the respondents expected the quality of the laboratory tests to be improved; however, 41.6% answered that the income of the referral clinic is expected to decrease. CONCLUSIONS: For the improvement of the medical insurance reimbursement system, the administrative fee for the referral clinic and the test fee for the independent medical laboratory should be reimbursed directly to the respective organizations. These changes could be made possible with the proper analysis of medical costs and the development of an effective EDI reimbursement system.

Detección del daño genotóxico agudo y crónico en una población de laboratoristas ocupacionalmente expuestos / Detection of acute and chronic genotoxic damage in an occupationally-exposed population

En el ámbito mundial se ha encontrado una fuerte relación entre la exposición a agentes genotóxicos y la incidencia de cáncer y problemas reproductivos, en personal ocupacionalmente expuesto. En el presente trabajo se evaluó, en personal vinculado a los laboratorios de la Universidad Nacional de Colombia, sede Medellín, el efecto de la exposición a agentes potencialmente genotóxicos, mediante las pruebas de intercambio de cromátides hermanas (ICH) y la electroforesis en gel de células individuales (prueba cometa). Se logró estandarizar herramientas metodológicas que permitieran cuantificar el daño producido por la exposición a agentes potencialmente genotóxicos e implementarlas en programas de monitorización para propósitos de salud ocupacional. La evaluación se realizó en dos poblaciones, una expuesta y una control, mediante el uso de muestras pareadas; para el apareamiento se eligieron individuos de la misma edad, género y hábitos. La prueba cometa mostró daño agudo en la población expuesta, mientras que la prueba de ICH no reveló daño crónico. De otro lado, se encontró que el índice de ICH en las dos poblaciones evaluadas no varió con los hábitos ni con el género, pero sí con la edad. Lo anterior muestra la utilidad de la prueba cometa para medir las exposiciones agudas y la del ICH como una excelente prueba para cuantificar las exposiciones crónicas; estas pruebas son imprescindibles como parte de la batería utilizada en estudios de Monitorización genotóxica. Mediante este estudio se adecuó la infraestructura y se capacitó al personal para llevar a cabo monitorizaciones sobre genotoxicidad con propósitos de salud ocupacional y con el ánimo de extender este servicio tanto a la comunidad universitaria como a los sectores público y privado

Worldwide studies in people occupationally exposed to genotoxic agents have shown a strong correlation of the exposition with cancer incidence and reproductive dysfunctions. This research evaluated, in laboratory personnel at the Universidad Nacional, Medellín, Colombia, the effect of exposition to potentially genotoxic agents, by means of sister chromatids interchange tests (SCI) and electrophoresis in single cells gel (comet assay). Standardization of methodological tools to quantify the damage produced by exposition to potentially genotoxic agents was achieved, in order to implement them in occupational health monitoring programs. Evaluation was carried out in two populations, exposed and control, using paired samples. Age, sex and habits were used as criterions for pairing. Comet assay showed punctual damage in the exposed population, while SCI test did not reveal chronic damage. On the other hand, neither habits nor sex showed relation with SCI index, but age did. The usefulness of the comet assay to measure the effect of punctual expositions, and that of SCI as an excellent test to quantify the effect of chronic expositions, makes them indispensable as part of the battery used in genotoxic monitoring studies. As part of the benefits of this research, infrastructure was adapted and some personnel was qualified to carry out occupational health genotoxic monitoring, with the aim of extending this service to the University community and to the private and public sectors

Construction and Application of Pathology Information System / 医疗卫生装备

Objective To develop a pathology information system and provide a pathology testing platform with digitalization,normalization and optimization. Methods Based on the principal and requirement of information engineering theory to analyze the profession,flow-sheet management and data needs of pathology information system. The pathology examination and related testing were analyzed mainly,included some special requirements in installation of work position,quality control,cost management,which were transformed conceptual and logical structure of database and realized physical composition on Oracle database. The reciprocal software codes were researched by PB program,which can build database in servers and install application software in front end computer. Results The system that was specified the components of the clinical data entry,pathology examination registry,clinical document repository,EMR application server and the e-node accessing server. The system was tested and the result indicated that the system was an effective and scalable. Conclusion The pathology information system can be not only used realize the sharing of EMR documents across multiple hospital,but also support the collection clinical data within hospital clinical system integration.