Consensus statement on the use of biosimilar drugs in immune-mediated diseases in Spain.

OBJECTIVE: To improve knowledge about biosimilar medicines and to generate a consensus framework on their use. METHODS: Qualitative study. A multidisciplinary group of experts in biosimilar medicines was established (1dermatologist, 1hospital pharmacist, 1rheumatologist, and 1gastroenterologist) who defined the sections and topics of the document. A narrative literature review was performed in Medline to identify articles on biosimilar medicines. Systematic reviews, controlled, pre-clinical, clinical, and real-life studies were selected. Based on the results of the review, several general principles and recommendations were generated. The level of agreement was tested in a Delphi that was extended to 66 health professionals who voted from 1 (totally disagree) to 10 (totally agree). Agreement was defined if at least 70% of the participants voted ≥7. RESULTS: The literature review included 555 articles. A total of 10 general principles and recommendations were voted upon. All reached the level of agreement established. The document includes data on the main characteristics of biosimilar medicines (definition, development, approval, indication extrapolation, interchangeability, financing, and traceability); published evidence (biosimilarity, efficacy, effectiveness, safety, immunogenicity, efficiency, switch); barriers and facilitators to its use; and data on information for patients. CONCLUSIONS: Authorized biosimilar medicines meet all the characteristics of quality, efficacy, and safety. They also significantly help improve patient access to biological therapies and contribute to health system sustainability.

Diversidad y estructura arbórea en afloramientos de carbonato de calcio en Calakmul, México / Tree diversity and structure in carbonate calcium banks in Calakmul, Mexico

Resumen Introducción: La vegetación arbórea de selvas que se desarrolla en ambientes kársticos dominados por carbonato de calcio enfrenta la restricción de agua y nutrientes, lo que condiciona su desarrollo. Objetivo: Analizar la composición, diversidad y estructura de la vegetación arbórea que se desarrolla en afloramientos de calcio (yesales) y sus condiciones edáficas comparándolas con las presentes en vegetación secundaria (VS). Métodos: Se emplearon 17 parcelas de 1 000 m², 14 en yesales y 3 en VS. Se obtuvo una muestra compuesta de suelo por parcela y estimamos pH, conductividad eléctrica (CE-salinidad), % de carbonatos de calcio (CaCO3), materia orgánica (MO), fósforo (P) y nitrógeno (N). La diferencia en la composición de especies se evaluó mediante un análisis de similitud (ANOSIM). Empleamos métodos de rarefacción y extrapolación, estimando la diversidad mediante los números de Hill (q = 0, q = 1 y q = 2). Se utilizó un análisis de regresión linear para evaluar la influencia de las características edáficas en la diversidad, el diámetro y la altura promedios. Resultados: Los suelos en yesales presentaron concentraciones bajas de MO, P y N, valores altos de CE-salinidad y altos porcentajes de CaCO3. Se registraron 6 443 individuos de 54 especies en yesales y 594 individuos de 62 especies en la VS, siendo la composición significativamente diferente. La diversidad, los valores promedio de altura y diámetro fueron menores en yesales respecto de VS, estas diferencias estuvieron relacionadas con las condiciones edáficas. Conclusiones: La vegetación arbórea en yesales tiene una composición semejante a la de selvas subperennifolias de Calakmul. Las tallas pequeñas de los árboles están relacionadas con el alto porcentaje de CaCO3 y los altos valores de CE que condicionan la disponibilidad de MO, N y P. Este estudio apoya la idea de que precarias condiciones edáficas tienen una influencia negativa en la diversidad y la estructura horizontal y vertical de la vegetación arbórea.

Abstract Introduction: Tree vegetation of forests that develops in karst environments dominated by calcium carbonate faces the restriction of water and nutrients, which negatively affects its development. Objective: Analyze the composition, diversity, and structure of tree vegetation that develops in calcium outcrops (yesales) and their edaphic conditions compared to those present in the adjacent secondary vegetation (VS). Methods: Plots of 1 000 m² were used, 14 in yesales and 3 in VS. For soil sampling, we obtained a sample composed of each plot, and estimate pH, electrical conductivity (EC-salinity), % of calcium carbonates (CaCO3), organic matter (OM), phosphorus (P) and nitrogen content (N). The difference in species composition was estimated by similarity analysis (ANOSIM). We used rarefaction and extrapolation methods to standardize sample, and estimate diversity by Hill numbers (q = 0, q = 1 and q = 2). Linear regression was used to determine the relative influence of edaphic characteristics in diversity, average diameter, and height. Results: Soils in yesales presented low concentrations of OM, P, and N, with high values of EC-salinity and high percentages of CaCO3. In yesales, 6 443 individuals were recorded in 54 species and in the secondary vegetation 594 individuals and 62 species, the species composition being significantly different between both conditions. Diversity, average values of height, and diameter were significantly lower in yesales regarding the secondary vegetation, these differences were significantly related to edaphic conditions. Conclusions: Tree vegetation in yesales has a composition like the sub-evergreen forests of Calakmul. Small sizes in the arboreal individuals are related to the high percentage of CaCO3 and the high EC values, which partly condition the low availability of OM, N and P affecting the growth of the trees. This study supports the idea that precarious edaphic conditions have a negative influence on the diversity and horizontal and vertical structure of tree vegetation.

Prueba de caminata de seis minutos ¿es posible predecir el consumo de oxígeno en personas con patologías? Una revisión bibliográfica / Six-Minute Walk Test. Is It Possible to Predict Oxygen Consumption in People with Pathologies? A Bibliographic Review / Teste de caminhada seis minutos. É possível prever o consumo de oxigênio em pessoas com patologia? Uma revisão bibliográfica

Resumen La prueba de caminata de seis minutos (PC6M) consiste en recorrer la mayor distancia posible y se caracteriza por ser una prueba de fácil realización. El objetivo de esta revisión fue examinar la relación entre las variables de distancia recorrida, patologías cardíacas, pulmonares y el consumo de oxígeno de una prueba de criterio en cinta rodante y/o cicloergómetro, y las ecuaciones de predicción del VO2 en la PC6M de Maldonado e Ingle (2006), Vanhelst (2013) y Costa (2017) para personas con patologías. El manuscrito es una revisión bibliográfica que utilizó las bases de datos Scopus y WOS, con artículos en inglés, español y portugués entre 2000 y 2017. La distancia es la variable que más se midió y que más se asoció con el VO2, encontrándose correlaciones significativas con valores de 0.01 hasta 0.8, las patologías más relacionadas con el VO2 máx. fueron la hipertensión pulmonar, enfermedad pulmonar obstructiva, insuficiencia cardíaca, disfunción sistólica ventricular y accidente cerebro-vascular y el cicloergómetro fue el más utilizado en las pruebas de criterio de VO2 máx. Solo una ecuación fue elaborada para niños que eran obesos la que incluyó distancia e IMC (Vanhelst), otra ecuación fue para adultos con enfermedad cardíaca que además incluía el sexo (Costa), una en pacientes con disfunción sistólica ventricular que aparte incorporó la edad, volumen espiratorio y hemoglobina (Ingle) y otra fórmula fue para adultos con insuficiencia cardíaca que consideró la distancia (Maldonado). Se sugiere utilizar la ecuación más apropiada y elaborar modelos predictivos para personas con diversas características.

Abstract The six-minute walk test (SMWT) consists of walking as far as possible and is characterized by being an easy test to perform. This paper examines the relationship between the variables of distance traveled, cardiac and pulmonary pathologies, and the oxygen consumption of a criterion test on treadmill and/or cycle ergometer, and the prediction equations of VO2 in the SMWT of Maldonado and Ingle (2006), Vanhelst (2013) and Costa (2017) for people with pathologies. The paper is a bibliographic review that used the Scopus and WOS databases containing articles in English, Spanish and Portuguese, published between 2000 and 2017. Distance is the variable that was most measured, and it was most associated with VO2; correlations with values from 0.01 to 0.8 were found. The pathologies most related to VO2 max were pulmonary hypertension, obstructive pulmonary disease, and ventricular heart failure and stroke; and the cycle ergometer was the most commonly used in the VO2 max criterion tests. Only one equation was created for children who were obese; it included distance and BMI (Vanhelst). Another equation was generated for adults with heart disease that also included sex (Costa). Besides, one equation was for patients with ventricular systolic dysfunction that also incorporated age, volume expiratory and hemoglobin (Ingle); another one was created for adults with heart failure, and this formula considered the distance (Maldonado). It is suggested to use the most appropriate equation and create predictive models for people with different characteristics.

Resumo O teste de caminhada de seis minutos (TC6M) consiste em andar o mais longe possível e é caracterizado como um teste fácil. O objetivo desta revisão foi examinar a relação entre as variáveis distância percorrida, patologias cardíacas, pulmonares e o consumo de oxigênio de um teste de critério em esteira e/ou ciclo ergômetro, e as equações de predição do VO 2 no TC6M de Maldonado e Ingle (2006), Vanhelst (2013) e Costa (2017) para pessoas com patologias. O manuscrito é uma revisão bibliográfica que utilizou as bases de dados Scopus e WOS, com artigos em inglês, espanhol e português entre 2000 e 2017. A distância é a variável mais medida e mais associada ao VO 2, encontrando correlações significativas com valores de 0,01 a 0,8, as patologias mais relacionadas ao VO 2 max. foram a hipertensão pulmonar, doença pulmonar obstrutiva, insuficiência cardíaca, disfunção sistólica ventricular e acidente vascular encefálico e o ciclo ergômetro foi o mais utilizado nos testes do critério VO 2 max. Apenas uma equação foi desenvolvida para crianças obesas, que incluíram distância e IMC (Vanhelst), outra equação foi para adultos com doença cardíaca que também incluiu sexo (Coast), uma em pacientes com disfunção sistólica ventricular que incorporaram a idade, volume expiratório e hemoglobina (Ingle) e outra fórmula foi para adultos com insuficiência cardíaca que considerou a distância (Maldonado). Sugere-se utilizar a equação mais adequada e desenvolver modelos preditivos para pessoas com características diversas.

Update on biosimilars in inflammatory bowel disease: Position and recommendations in Mexico. / Actualización sobre los medicamentos biocomparables en la enfermedad inflamatoria intestinal: posición y recomendación en México.

The biotechnology-derived medicines known as biosimilars are defined as non-originator treatments that have demonstrated quality, efficacy, and safety comparable to the reference biologic drug. Clinical trials have shown that the infliximab biosimilar, CT-P13, and the candidates for the adalimumab biosimilars, ABP 501 and ZRC 3197, are not significantly different, with respect to efficacy and safety, from the originator drugs in patients with other autoimmune diseases. However, controversy has arisen over the use of biosimilars in inflammatory bowel disease, due to the incipient evidence not only in patients with no previous biotechnology treatment, but also in patients in remission, that could be switched to a biosimilar for non-medical reasons. The present review is the first critical analysis by different specialists in the area of gastroenterology on the use of biosimilars in inflammatory bowel disease, the evidence on interchangeability, the extrapolation of indications, efficacy, safety, immunogenicity, and the clinical impact of the Mexican health regulations. The aim of our review was to make the positioning and recommendations of these new therapeutic options known, given that they have a potential cost-benefit for both patients and healthcare institutions.

Extrapolating cetacean densities to quantitatively assess human impacts on populations in the high seas.

As human activities expand beyond national jurisdictions to the high seas, there is an increasing need to consider anthropogenic impacts to species inhabiting these waters. The current scarcity of scientific observations of cetaceans in the high seas impedes the assessment of population-level impacts of these activities. We developed plausible density estimates to facilitate a quantitative assessment of anthropogenic impacts on cetacean populations in these waters. Our study region extended from a well-surveyed region within the U.S. Exclusive Economic Zone into a large region of the western North Atlantic sparsely surveyed for cetaceans. We modeled densities of 15 cetacean taxa with available line transect survey data and habitat covariates and extrapolated predictions to sparsely surveyed regions. We formulated models to reduce the extent of extrapolation beyond covariate ranges, and constrained them to model simple and generalizable relationships. To evaluate confidence in the predictions, we mapped where predictions were made outside sampled covariate ranges, examined alternate models, and compared predicted densities with maps of sightings from sources that could not be integrated into our models. Confidence levels in model results depended on the taxon and geographic area and highlighted the need for additional surveying in environmentally distinct areas. With application of necessary caution, our density estimates can inform management needs in the high seas, such as the quantification of potential cetacean interactions with military training exercises, shipping, fisheries, and deep-sea mining and be used to delineate areas of special biological significance in international waters. Our approach is generally applicable to other marine taxa and geographic regions for which management will be implemented but data are sparse.

El papel de los biosimilares en la enfermedad inflamatoria intestinal: una realidad en nuestro país / The Role of Biosimilars in Inflammatory Bowel Disease: A Reality in our Country

Resumen La enfermedad inflamatoria intestinal (EII) es un término con el que se conocen varias entidades, las 2 más importantes son: la colitis ulcerativa idiopática (CUI) y la enfermedad de Crohn (EC), cuyo origen es multifactorial y se caracterizan por un fenómeno inflamatorio, crónico, recurrente con diferentes grados de severidad del tubo digestivo; pero además con afectación potencial de otros órganos. En la última década ha habido un renovado interés en dichas entidades, debido a una incidencia creciente de estas, pero también debido al desarrollo de medicamentos que por primera vez están cambiando la historia natural de estas enfermedades: son los medicamentos llamados biológicos, que son aquellos producidos o derivados de organismos vivos y representan el sector de mayor crecimiento en la industria farmacéutica mundial. Debido al interés comercial, se han desarrollado y sometido a las autoridades reguladoras productos no originadores; similares, pero no idénticos a los productos de referencia. La Agencia Europea de Medicamentos (EMA) aprobó el primer biosimilar del infliximab para todas las indicaciones en las cuales este estaba aprobado, incluidas: colitis ulcerativa moderada a severa en todas las edades, EC moderada a severa en todas las edades, al igual que EC fistulizante, artritis psoriásica (AP), psoriasis, espondilitis anquilosante (EA) y artritis reumatoide (AR) (1). En esta revisión nos proponemos definir lo que son estos productos al igual que algunos conceptos relacionados (extrapolación, sustitución e intercambiabilidad), además hacer una revisión histórica de su desarrollo, sus indicaciones actuales, las posiciones de las diferentes asociaciones científicas al respecto y, lo más importante, brindar datos de la vida real en cuanto a su efectividad, seguridad y costos en los diferentes países donde se han estado usando.

Abstract The term Inflammatory Bowel Disease (IBD) is used to identify several entities, the two most important of which are Idiopathic Ulcerative Colitis (IUC) and Crohn's Disease (EC). Both are multifactorial in origin, are chronic and recurrent, are characterized by inflammation, have varying degrees of severity, and potentially involve other organs. In the last decade there has been renewed interest in these entities due to growing incidence and to the development of drugs called biologicals. For the first time, these drugs have changed the natural history of these diseases. They are produced or derived from living organisms and represent the fastest growing sector in the global pharmaceutical industry. Due to commercial interest, products similar but not identical to the original products have been developed and submitted to regulatory authorities. The European Medicines Agency has approved the first biosimilar for infliximab for all indications for which it has been approved. These include moderate to severe ulcerative colitis (UC) at all ages, moderate to severe Crohn's disease (CD) at all ages, fistulizing Crohn's disease, Psoriasic arthritis, Psoriasis, Ankylosing Spondylitis, and Rheumatoid Arthritis. 1 In this review, we define what these products are, as well as some concepts coined for their usage including extrapolation, substitution and interchangeability. We also make a historical review of their development, current indications, the positions of various scientific associations with respect to them, and - most importantly - provide real-life data regarding their effectiveness, safety and costs in countries where they have been used.

Acute silver toxicity to Cnesterodon decemmaculatus (Pisces: Poeciliidae) in a river with extreme water-quality characteristics / Toxicidad aguda de la plata sobre Cnesterodon decemmaculatus (Pisces: Poeciliidae) en un río con características extremas de calidad de agua

Abstract. A 96 h acute silver toxicity test was performed in order to determine silver toxicity (LC50) to a local fish species (Cnesterodon decemmaculatus) in a river with extreme water-quality characteristics (Pilcomayo River, South America) and evaluate a cross-fish-species extrapolation of the Biotic Ligand Model. The dissolved silver concentrations tested were 0.095, 0.148, 0.175 and 0.285 mg Ag L−1. The 96 h Ag LC50 calculated for C. decemmaculatus was 0.14 mg L−1 (0.18 - 0.10) and the value predicted by BLM for Pimephales promelas was 0.051 mg Ag L−1. Test water elevated hardness may have exerted some protective effect. High mean water pH may have exerted a major protective effect by reducing silver free ion form and causing silver precipitation. The mortality pattern observed in this toxicity test may lend some support to a relationship between gill silver accumulation and mortality. A cross-fish-species extrapolation of Ag BLM for P. promelas was not valid in Pilcomayo River water and experimental conditions of this toxicity test.

Con el objeto de determinar la toxicidad de la plata en un pez nativo (Cnesterodon decemmaculatus), se llevó a cabo un ensayo estático de toxicidad aguda a 96 horas en un agua natural con características de calidad de agua, extremas (río Pilcomayo, Sudamérica). Asimismo, se evaluó una posible extrapolación inter-especie del Modelo del Ligando Biótico en el agua experimental. La concentración inicial de plata en solución en los distintos tratamientos fue de 0,095; 0,148; 0,175 y 0,285 mg Ag L −1 . La CL50 a las 96 horas calculada para C. decemmaculatus fue de 0,14 (0.18 - 0.10) mg Ag L−1 y el valor predicho por el BLM para Pimephales promelas fue de 0,051 mg Ag L−1. La elevada dureza del agua experimental pudo haber tenido algún efecto protector frente a la toxicidad de la plata. El valor medio de pH del ensayo fue elevado y posiblemente tuvo un gran efecto protector por reducción de la forma iónica libre y precipitación del metal. El patrón de mortalidad observado en este ensayo de toxicidad apoyaría la relación causa-efecto entre acumulación de plata en las branquias y mortalidad. La extrapolación inter-especie del BLM para P. promelas no resultó válida en el agua del río Pilcomayo y en las condiciones experimentales de este ensayo.

Avaliação dos níveis séricos de lactato em cães submetidos a anestesia dissociativa / Evaluación de los niveles séricos de lactato en perros sometidos a anestesia dissociativa / Seric level assessment of lactate in dogs submitted to dissociative anesthesia

A mensuração da lactatemia como indicador indireto da oxigenação dos tecidos e, por conseguinte, de estresse e acidemia, tem potencial para se tornar uma ferramenta muito útil em medicina veterinária. Neste estudo, 10 cães domésticos adultos clinicamente saudáveis foram anestesiados pela associação de tiletamina, zolazepam, xilazina e atropina, em doses calculadas por meio de extrapolação alométrica intraespecífica. A lactatemia foi mensurada por meio de reação enzimática, com leitura por fotometria de reflectância, 1.140 minutos e um minuto antes da administração da associação anestésica por via intramuscular, aos 10, 20, 40, 60, 80, 180, 360, 720, 1.140, 2.880 e 14.440 minutos após a injeção. O comportamento das concentrações de lactato frente aos eventos experimentais evidenciou normalidade antes e depois da anestesia, e queda significativa durante a mesma. Concluiu-se que a anestesia dissociativa pela associação de tiletamina, zolazepam, xilazina e atropina, em doses calculadas por meio de extrapolação alométrica intraespecífica, não eleva a lactatemia. De fato, durante a anestesia ocorreu queda significativa das concentrações de lactato em relação aos níveis considerados basais.

Lactate level measuring as an indirect indicator of tissue oxygenation, and consequently stress and acidemia, isa potentially useful tool for Veterinary Medicine. In this study 10 adult healthy dogs were anesthetized with the combination of tiletamine, zolazepam, xylazine and atropine, with dosages calculated by intraespecific allometric scaling. Blood lactate was measured by enzymatic reaction with reflectancy photometry 1.140 and one minute before intramuscular administration of the anesthetic combination, and at 10, 20, 40, 60, 80, 180, 360, 720, 1,140, 2.880 and 14.440 minutes after the injection. Serum lactate concentrations were normal prior and after anesthesia, and presented significant decrease throughout it. It was concluded that the combination of tiletamina, zolazepam, xylazine and atropine in allometrically scaled dosages do not increase lactatemia. In fact, significant decrease of lactate serum concentrations in comparison with basal levels was observed during anesthesia.

La mensuración de la lactatemia como indicador indirecto de la oxigenación de los tejidos, así como de estrés y acidemia, tiene potencial para tornarse una herramienta muy útil en medicina veterinaria. En este estudio fueron anestesiados 10 perros adultos saludables con la asociación de tiletamina, zolazepam, xilacina y atropina, en dosis calculadas por medio de extrapolación alométrica intraespecífica. La lactatemia fue mensurada por medio de reacción enzimática, con evaluación porfotometría de reflectancia, 1.140 minutos y un minuto antes de la suministración de la combinación anestésica por vía intramuscular,y a los 10, 20, 40, 60, 80, 180, 360, 720, 1.140, 2.880 y 14.440 minutos después de la inyección. El comportamiento de las concentraciones de lactato delante de los eventos experimentales evidenció normalidad antes y después de la anestesia, y caída significativa durante la misma. Se concluyó que la anestesia disociativa por la combinación de tiletamina, zolazepam, xilacina y atropina, en dosis calculadas por medio de extrapolación alométrica intraespecífica, no eleva la lactatemia. De facto, durante la anestesia ocurrió caída significativa de las concentraciones de lactato en relación a los niveles considerados basales.

Neurolepsia prolongada com decanoato de haloperidol no tratamento de dermatite psicogênica em um cão doméstico (Canis familiaris, 1758) / Long-term Neurolepsy with Haloperidol Decanoate in the Treatment of Psychogenic Dermatitis in a Domestic Dog (Canis Familiaris, 1758) / Neurolepsia de largo plazo con decanoato de haloperidol en el tratamiento de dermatitis psicogénica en un perro (canis familiaris 1758)

Relata-se o tratamento de um caso de dermatite psicogênica em um cão Rottweiler macho, com idade de 13 meses, pesando 42 kg. O paciente apresentava graves lesões dermatológicas devidas a auto-mutilação por lambedura, em ambas as regiões metatarsianas, e a anamnese indicava que o distúrbio psíquico tivesse origem no estresse provocado por uma mudança ambiental. Prescreveu-se tratamento com um neuroléptico de ação prolongada, o decanoato de haloperidol, com dose calculada por meio de extrapolação alométrica interespecífica, usando-se como modelo a dose total humana de 100 mg/70 kg. A dose total calculada para o cão de 42 kg foi de 70 mg, sendo administrada semanalmente, durante seis semanas. Já na segunda semana a recuperação era satisfatória, sendo que a cura completa foi obtida no 28º dia de tratamento. Mantido em observação por um período de seis meses, o paciente não apresentou quaisquer sinais de recidiva. Os resultados indicam que a droga apresenta excelentes perspectivas para o tratamento desta dermatopatia canina, e que o método de extrapolação alométrica interespecífica é plenamente eficiente no estabelecimento de protocolos posológicos individualizados.

ABSTRACT: This paper reports the results of the treatment of a 13 month-old male Rottweiler dog, weighing 42 kg, affected by psychogenic dermatitis. The patient presented serious cutaneous lesions due to self-licking, affecting both metatarsal areas. Anamnesis indicated that the psychic disturbance was caused by stress provoked by an environmental change. It was prescribed haloperidol decanoate, a long-acting neuroleptic, with dose calculated by interspecifi c allometric scaling, using as model the human total dose of 100 mg/70 kg. The total dose calculated for the 42 kg dog was 70 mg, and it was administered weekly for six weeks. Clinical recovery was already satisfactory in the second week, and complete cure was obtained in the 28th day of treatment. The patient was monitored by a six months period and did not present any relapsing signs. The results indicate that the drug presents excellent perspectives for the treatment of this canine skin disease, and that the method of interespecifi c allometric scaling is effi cient in the establishment of individualized therapeutic protocols.KEY WORDS: psychogenic dermatitis, neuroleptic, haloperidol decanoate, allometric scaling, dog

RESUMEN: Relata-se el tratamiento de un caso de dermatitis psicogénica en un perro Rottweiler macho, con edad de 13 meses y peso de 42 kg. El paciente presentaba graves lesiones dermatológicas debidas a auto-mutilación por lamedura, en ambas las regiones metatarsianas, y la anamnesia indicaba que la enfermedad tuviese origen en el estrés provocado por un cambio ambiental. Se prescribió tratamiento con un agente neuroléptico de acción prolongada, el decanoato de haloperidol, con dosis calculada por extrapolación alométrica interespecífi ca, se usando como modelo la dosis total humana de 100 mg/70 kg. La dosis total calculada para el perro de 42 kg fue de 70 mg, sendo administrada semanalmente, durante seis semanas. La recuperación clínica ya era satisfactoria en la segunda semana, y la cura completa se obtuvo en el vigésimo octavo día de tratamiento. El paciente fue supervisado por un periodo de seis meses y no presentó ninguna señal de retorno de la enfermedad. Los resultados indican que la droga presenta perspectivas excelentes para el tratamiento de esta enfermedad en perros, y que el método de extrapolación alométrica descascarar es en el establecimiento de protocolos terapéuticos individualizados.