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.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer:Extraction of active ingredients as an example / 药物分析学报

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Avaliação da presença de fármacos em lodo de estação de tratamento de esgotos, antes e após processo de biorremediação por compostagem / Evaluation of the presence of drugs in sewage treatment station sludge before and after the bioremediation process by composting

Resumo A presença de fármacos residuais no ambiente é um problema crescente e de abrangência global, com ampla quantidade de pesquisas visando sua quantificação. Porém, seu comportamento e efeitos, tanto no ambiente quanto para o ser humano, ainda não são bem conhecidos. Neste trabalho foram avaliados sete fármacos: Atenolol, Carbamazepina, Clonazepan, Ibuprofeno, Paracetamol, Sinvastatina e Fluoxetina, em amostras de lodo proveniente de uma estação de tratamento de esgotos do sistema público. A extração dos compostos na matriz foi baseada na sua lixiviação em água e a quantificação analítica foi determinada por um sistema de cromatógrafo líquido de ultra performance, acoplado ao espectrômetro de massas. Os resultados indicam a possível movimentação de alguns fármacos da fase aquosa para a sólida. Observou-se que a compostagem do lodo pode favorecer a biodegradação ou mobilização dos compostos, pois houve redução significativa nas concentrações, quando comparados os valores obtidos antes e após o processo de compostagem. A não detecção de um composto não significa necessariamente que ele tenha sido degradado por microrganismos, entretanto, estudos pretéritos chegaram a resultados semelhantes, o que corrobora para a adequação da proposta metodológica e dos procedimentos adotados, contribuindo para a produção de resultados confiáveis.

Abstract The presence of residual drugs in the environment is a growing global issue, with many studies seeking to quantify it. However, its behavior and effects, both on the environment and on humans are still mostly unknown. In this study, seven drugs were evaluated: Atenolol, Carbamazepine, Clonazepam, Ibuprofen, Paracetamol, Simvastatin, and Fluoxetine, from samples of sludge from a sewage treatment plant of the public system. The extraction of the compounds from the matrix was based on the leaching of the compounds in water and the analytical quantification was determined by an ultra-performance liquid chromatograph system, coupled to the mass spectrometer. The data indicate the possible movement of some drugs from aqueous to solid phase. We observed that the composting of the sludge could favor the biodegradation or mobilization of the compounds since there was a significant reduction in the concentrations, when comparing the values obtained before and after the composting process. The non-detection of a compound does not necessarily mean that it has been fully degraded by microorganisms; however, past studies reached similar results, which corroborates the adequacy of the methodological proposal and the adopted procedures, contributing to the production of reliable results.

The Quality of Logistics Management Information System and the Availability of Tracer Drugs at Health Posts in Rural Ethiopia: A Mixed-Method Study

BACKGROUND: Proper implementation of the logistics management information system (LMIS) would facilitate access to essential pharmaceutical products. It also prevents wastage at health posts. The aim of this study was to assess the implementation of the LMIS and the availability of tracer drugs at health posts in rural Ethiopia. METHODS: We employed a cross-sectional descriptive design with a mixed-method approach. The data used for this paper was collected from March to May 2019 as part of the National HEP assessment. The study involved 343 health posts randomly selected from nine regions of Ethiopia. Women's Development Army members and household heads participated in the qualitative study (i.e. in FGD and KII). The quantitative data were exported from Open Data Kit (ODK) to Stata 15.1 for statistical analysis, and the qualitative data were entered into NVivo 12 and analyzed using thematic content analysis. RESULTS: Of the health posts, 59.4% had a space for storing drugs; less than half (41.9%; 95% confidence interval (CI) [36%, 48%]) had a functioning refrigerator. The mean percentage of the availability of selected tracer drugs at health posts was 59.6%, with a 95% CI (58.9%, 60.3%). Bin cards were available at 43% (95% CI [40%, 46%]) of health posts, and among these, only 27.5% of the health posts adequately used the bin cards. CONCLUSION: The absence and poor use of LMIS tools was observed at health posts. Proper implementation of the LMIS has the potential to improve the availability of essential drugs that, in turn, improve health post level delivery of health services.

Assignment based learning of different dosage form and newer and targeted drug delivery system among undergraduate students

Background: Knowledge of newer and targeted drug delivery system is essential for applying pharmacology in treating various clinical conditions. Using appropriate dosage form considering patient抯 age, comorbidities, socioeconomic status, literacy, severity of clinical condition will enhance the effect of drug, decrease the adverse reactions and improve the patient抯 compliance. Learning is most effective when student involvement, participation, and interaction is maximized. Aim and Objectives: To evaluate improvement in knowledge of 2nd year MBBS students for availability, use and necessity of different dosage forms and newer and targeted drug delivery system by assignment based learning. Materials and Methods: The assignment-based activity was conducted for 2nd year MBBS students on different dosage forms and newer and targeted drug delivery system. Seventy students were divided into seven groups and assigned seven questions. Pre-test and post-test were conducted. Results: Post-test results were significantly higher than the pre-test results when compared by paired t-test. There was significant difference among the groups when Analysis of variance test was applied. Group 3, 4, 5 and 6 had gathered good information from e-resources about different drugs list of newer and targeted drug delivery system and Group 3 and 4 gathered details of liposomal and radio-pharmaceuticals based newer drug delivery system. Conclusion: Assignment based activities should be carried out for the critical topics where recent advances are going on, newer techniques for treatment are developing and newer dosage forms are marketed. Through this activity students with poor performance can be identified and guided personally and encouraged for better performance to be a competent physician.

Evolution of modern age drug discovery of lipopeptides and computer-aided drug discovery in India

The endeavor has been attempted to present a review on the evolution of modern age drug discovery in India. The contribution of next generation therapeutics options microbial metabolites and the computational drug discovery aspects to the global market from India have been represented. Microbial metabolites such as lipopeptides and peptide therapeutics are gaining worldwide importance due to their multiple applications as broad-spectrum antimicrobial, antiviral, anticancer properties etc. Due to the surge of microbial resistance, tumor resistance, and ongoing pandemic due to constantly mutating corona virus, there is a need to develop next-generation therapeutics options from natural origin, less toxic to the environment, and have higher specificity towards target. Small molecule therapeutics are certainly less specific towards cancer targets hence the cytotoxicity is a major issue in cancer treatment while drug resistance due to the mutations are coming as challenges every day for drug discovery researchers. Microbial lipopeptide reserves a sweet spot in between the small molecule inhibitors and peptide therapeutics because of their amphiphilic compounds consist of a fatty acid side chain and a cyclic peptide moiety of hydrophilic nature. The computational drug discovery approach accelerates the drug discovery process due to the advancement in supercomputer facilities provided by various funding agencies such as the Department of Biotechnology (DBT) and the Department of Science and Technology (DST) in India. The current review article is focusing light on the research contribution of Indian Scientists and Govt. of India in the field of lipopeptide-based research and applications of Computer-aided drug discovery.

A contribuição da logística para o fortalecimento da produção nacional e para o acesso universal no âmbito do SUS / The contribution of logistics to the strengthening of national production and universal access in the scope of the Unified Health System

RESUMO Objetivou-se apontar os elementos essenciais da logística que contribuem para a promoção do acesso no contexto do sistema produtivo da saúde, visando articular a produção nacional, reduzir a dependência externa para viabilizar o acesso universal e o fortalecimento do Sistema Único de Saúde (SUS) em um contexto de pandemia e crise sanitária. Utilizou-se como estratégia metodológica uma pesquisa qualitativa de base bibliográfica sobre os conceitos de sistemas de saúde, saúde pública e acesso a medicamentos e vacinas, somados ao perfil dos operadores logísticos nacionais e à operacionalização do plano nacional de imunização contra a Covid-19 do Ministério da Saúde. Concluiu-se que a logística desempenha papel fundamental na promoção do acesso às tecnologias em saúde, sendo necessário empreender esforços em pesquisas que incluam os atores do setor produtivo capazes de contribuir com a elaboração de políticas públicas na área da saúde. Os elementos centrais da logística precisam ser ressaltados para o fortalecimento de uma agenda que articule o Complexo Econômico-Industrial da Saúde com o acesso universal, pensando nos fatores logísticos como elementos críticos sem os quais o acesso não se materializa. É necessário que os sistemas logísticos sejam pensados como recurso dos sistemas de saúde para viabilizar sua integralidade e sustentabilidade.

ABSTRACT The objective was to point out the essential elements of logistics that contribute to the promotion of access in the context of the health production system to articulate national production, reduce external dependence to enable universal access and the strengthening of the Unified Health System (SUS) in the context of the pandemic and health crisis. Qualitative bibliographic-based research was used as a methodological strategy on the concepts of health system, public health, access to medicines, added to the profile of national logistics operators and the operationalization of the Ministry of Health's national immunization plan against COVID-19. It was concluded that logistics plays a fundamental role in promoting access to health technologies and it is necessary to undertake research efforts that include the actors of the productive sector capable of contributing to the elaboration of public policies in the field of health. The central elements of logistics need to be highlighted in order to strengthen an agenda that articulates the Health Economic-Industrial Complex with universal access, considering logistical factors as critical elements without which access does not materialize. Logistical systems should be thought of as a resource of universal health systems to enable their integrality and sustainability.

Cytochrome P450s in algae: Bioactive natural product biosynthesis and light-driven bioproduction

Algae are a large group of photosynthetic organisms responsible for approximately half of the earth's total photosynthesis. In addition to their fundamental ecological roles as oxygen producers and as the food base for almost all aquatic life, algae are also a rich source of bioactive natural products, including several clinical drugs. Cytochrome P450 enzymes (P450s) are a superfamily of biocatalysts that are extensively involved in natural product biosynthesis by mediating various types of reactions. In the post-genome era, a growing number of P450 genes have been discovered from algae, indicating their important roles in algal life-cycle. However, the functional studies of algal P450s remain limited. Benefitting from the recent technical advances in algae cultivation and genetic manipulation, the researches on P450s in algal natural product biosynthesis have been approaching to a new stage. Moreover, some photoautotrophic algae have been developed into "photo-bioreactors" for heterologous P450s to produce high-value added pharmaceuticals and chemicals in a carbon-neutral or carbon-negative manner. Here, we comprehensively review these advances of P450 studies in algae from 2000 to 2021.

A retrospective review of calls to the Poisons Information Helpline of the Western Cape during the first 6 months of the COVID-19 pandemic in South Africa

Background: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, poison centres worldwide have reported an increase in exposures to chemicals used for infection prevention. Increased availability and use could lead to an increase in exposures. Potential effects on a South African Poison Information Helpline were unknown, therefore a study was performed to describe changes in call volume and profile of poison exposures. Methods: A retrospective analysis was conducted on an observational database of telephone enquiries. All human-related poisoning exposure call data collected from 01 March to 31 August during 2018, 2019 and 2020 were extracted and analyzed. Summary statistics were used to describe all variables. Results: The total number of calls were 5137, 5508, and 5181 in 2018, 2019, 2020, respectively. The monthly call number during 2020 was mostly less than in 2019. More calls were received from the public calls (39.4% vs 33.1%) and for accidental exposures (65.6% vs 62.3%) increased during 2020 compared to 2019. Exposures to pharmaceuticals decreased by 14.8% from 2019 to 2020, while exposures to eucalyptus oil more than doubled from 21 in 2019 to 43 during 2020. Exposures to antiseptics and disinfectants increased by 60.4%, mainly due to hand sanitizers exposure which showed a 26-fold increase from 2019 (n = 6) to 2020 (n = 156). Conclusion: A change in the profile of poison exposures was observed during the COVID-19 pandemic. Lockdown regulations and greater availability of antiseptics and disinfectants probably led to the increase in exposures. Although symptoms were mostly mild, the public should be educated on safe storage and proper use of all chemicals.

Análisis de riesgo de un microorganismo objetable en un suplemento dietario para la liberación de lotes

RESUMEN La contaminación con microorganismos objetables en los productos farmacéuticos no estériles puede tener el potencial de disminuir o inactivar la actividad farmacológica y terapéutica del principio activo y por ende representar un peligro de gran riesgo para la salud de la persona que está en tratamiento con fármacos; adicionalmente la presencia de estos microorganismos dependiendo de su capacidad para producir enfermedad en huéspedes susceptibles pueden ocasionar infecciones no esperadas o enfermedades que afecten al paciente o consumidor de estos medicamentos no estériles. El objetivo del trabajo fue desarrollar un análisis de riesgo microbiológico de microorganismos objetables en un suplemento dietario de una industria farmacéutica como herramienta en la gestión de seguridad. La metodología fue observacional-descriptivo de corte transverso. En la industria farmacéutica (en el suplemento dietario) se desarrolló un análisis de riesgo estudiando todos los parámetros, teniendo como resultado, que las cápsulas blandas con aceite de Krill, no presentan microorganismo objetable del tipo patógeno, como producto de bajo riesgo, por lo que es aprobado para la liberación del lote siguiendo estos parámetros. En Paraguay no existen normativas acerca del análisis de microorganismos objetables, en comparación con otros países como Argentina, y desde hace tiempo en EE. UU y países europeos (por reportes de la FDA) por lo cual, este trabajo es relevante y de vital importancia para establecer legislaciones nacionales con miras a la fabricación de medicamentos seguros, confiables y eficaces.

ABSTRACT Contamination with objectionable microorganisms in non sterile pharmaceutical products may have the potential to decrease or inactivate the pharmacological and therapeutic activity of the active principle and therefore represent a danger of great risk to the health of the person who is being treated with drugs, additionally, the presence of these microorganisms, depending on their ability to produce disease in susceptible hosts, can cause unexpected infections or diseases that affect the patient or consumer of these non sterile drugs. The objective of the work was to develop a microbiological risk analysis of objectionable microorganisms in a dietary supplement of a pharmaceutical industry as a tool in safety management. This was an observational-descriptive cross-sectional study. In the pharmaceutical industry (in the dietary supplement) a risk analysis was developed studying all the parameters, having as a result that the soft capsules with Krill oil do not present objectionable microorganisms of the pathogenic type, as a low risk product, therefore it is approved for batch release following these parameters. In Paraguay there are no regulations about the analysis of objectionable microorganisms, in comparison with other countries such as Argentina, and for a long time in the US and European countries (due to FDA reports). Therefore, this work is relevant and very vital important to establish national legislation with a view of the manufacture of safe, reliable and effective drugs.

Socioeconomic impact of high-cost drugs in Brazilian dermatology. Legal and financial aspects, and impact on clinical practice

Abstract The technological advancement of the pharmaceutical industry, resulting from the techniques of molecular biology and expansion of the knowledge of immunopathogenesis, has modified the therapeutic arsenal used in dermatology. Scientific research and regulatory standards cause drug costs to rise, thus making their use impossible in most public policies. In order to make high-cost drugs viable in the public health network, the Specialized Pharmaceutical Assistance Component was created. However, despite the frequent incorporation of medications, the constant requirement of drugs through lawsuits leads to exorbitant costs to the state budget. The present work analyzed through a descriptive observational study, the current situation of the Specialized Component and the involvement of medicines used in dermatology, through legal reviews, financial analyses, and medical articles, aiming at future incorporations for the specialty. When assessing the legal demands for dermatological drugs in the state of São Paulo, the specialty still has a low participation and psoriasis is the main disease involved in requiring drugs through the judicial system in the state. New methods of access to raw materials must be created to reduce legal issues. Cost-effectiveness and public planning studies are mandatory for incorporating new dermatological therapies.

Analysis of Decision-making Data for Payment of Adverse Drug Reaction Relief System to Over-the-counter Drugs to Promote Their Proper Use / 社会薬学

Adverse Drug Reaction Relief System is intended for people who suffer adverse health effects from drugs despite their proper use, including over-the-counter (OTC) drugs. The decision-making data for the payment of relief benefits associated with OTC drugs and the instructions-for-use provided by community pharmacists and registered retailers were investigated. The results showed that the relief benefit nonpayment rate for OTC drugs was 3.9% and the number of cases was 9, of which 5 were due to improper use. Among the OTC drugs covered by relief benefits, the most common were schedule II pharmaceuticals, which were sometimes used in combination with prescription drugs. These results suggest that pharmacists and registered retailers should check for the use of concomitant drugs (e.g., with drug notebooks) at the time of the OTC drug sale. Pharmacists and registered retailers should provide a detailed explanation of the drugs to consumers and confirm that the information is understood, especially when schedule II pharmaceuticals or psychotropic drugs are sold. Additionally, information on the initial symptoms of an adverse drug reaction and treatment should be provided to prevent serious reactions. Follow-up with consumers during OTC drug use may also reduce the risk of misuse.

Probing the degradation of pharmaceuticals in urine using MFC and studying their removal efficiency by UPLC-MS/MS / 药物分析学报

Nutrient recovery from source-separated human urine has attracted interest as it is rich in nitrogen and phosphorus that can be utilized as fertilizer.However,urine also contains pharmaceuticals,steroid hormones,etc.and their removal is crucial as they have detrimental effects on the environment and human health.The current study focuses on investigating the degradation of pharmaceuticals using a double-chamber microbial fuel cell (MFC).Urine was spiked with four pharmaceuticals (trimethoprim,lamivudine,levofloxacin,and estrone) at a concentration of 2 μg/mL.The MFC was operated for 7 months in batch mode with this spiked urine as feed.The degradation efficiency of the MFC was studied,for which a selective liquid chromatography-tandem mass-spectrometric method was developed for the quantitation of compounds used in the spiking experiments and was validated with a lower limit of quantification of 0.39 ng/mL.The maximum removal rate achieved was 96％± 2％.The degradation mechanism involved processes like sorption and anoxic biodegradation.The voltage curve obtained showed that the presence of pharmaceuticals had an initial negative impact on power generation along with increased organic content;however,after the reactor acclimatization,increased power output was achieved with maximum organics removal at 30 h of retention time.This work opens a new perspective for the anoxic biodegradation of pharmaceuticals and can be useful in future bioremediation studies.

Taxas de descontinuação do tratamento após a troca de um biológico originador por um biossimilar em pacientes com doenças inflamatórias intestinais: revisão sistemática e metanálise / Discontinuation rates following a switch from a reference to a biosimilar biologic in patients with inflammatory bowel disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

RESUMO CONTEXTO: Os biológicos revolucionaram o tratamento da doença inflamatória intestinal (DII). Ademais, esses medicamentos influenciaram os custos relacionados ao tratamento. Tal aumento significativo nos gastos com o tratamento motivou desenvolvimento dos biossimilares. OBJETIVO: Esta revisão sistemática e metanálise objetivou avaliar a taxa de descontinuação de medicamentos na população com DII que foi submetida à troca do biológico originador para um biossimilar, em estudos observacionais que abordaram possíveis razões para a descontinuação do tratamento. MÉTODOS: Tendo como base de dados Medline (via PubMed), EMBASE, Cochrane Library e resumos de congressos médicos, foram rastreados artigos com relatos de troca de um biológico originador por um biossimilar, com acompanhamento pós-troca de no mínimo 6 meses ou três infusões. Todas as informações disponíveis sobre as taxas de descontinuação foram avaliadas. RESULTADOS: Foram incluídos no total 30 estudos observacionais, envolvendo 3.594 pacientes com DII. Vinte e seis estudos relataram uma mudança do infliximabe para CT-P13, dois estudos envolveram uma mudança para o SB2, e as informações sobre a troca não estavam disponíveis em dois estudos. As taxas de descontinuação foram de 8%, 14% e 21% aos 6, 12 e 24 meses, respectivamente. Os principais motivos para a descontinuação do medicamento e seus respectivos riscos foram: agravamento da doença (2%), remissão (4%), perda de adesão (4%), eventos adversos (5%) e perda de resposta (7%). A qualidade da evidência variou de baixa a muito baixa, dependendo do resultado analisado. Os sintomas subjetivos que levaram à descontinuação do medicamento foram relatados com pouca frequência, e o efeito nocebo foi claramente avaliado em apenas um dos artigos incluídos. CONCLUSÃO: As taxas de descontinuação após a mudança para um biossimilar em pacientes com DII aumentam com o tempo. No entanto, não foi possível confirmar o efeito nocebo como motivo da descontinuação. Portanto, ainda são necessários estudos em longo prazo avaliando o uso de biossimilares para monitorar eventos adversos e potenciais efeitos nocebo na vigilância pós-comercialização.

Immunopharmacology 2020. V International Congress on Immunopharmacology

The Organizing Committee of the V International Congress on Immunopharmacology (Immunopharmacology 2020) organized by the Cuban Society of Pharmacology, BioCubaFarma and the International Union of Basic and Clinical Pharmacology (IUPHAR) would like to invite you to participate in this important event, scheduled for June 9 to 13, 2020 at the Convention Centre of the Melia Marina Varadero Hotel, Varadero Beach, Matanzas, Cuba. The Congress will be formed by different workshops and symposia such as: Fifth workshop on new advances in immunopharmacology Fifth workshop on neuroimmunology, neuroimmunopharmacology and neuroimmunomodulation. Immunopharmacology of brain tumors Symposium on hereditary ataxias Fifth symposium on pharmacology of cytochrome P450 and transporters Fourth symposium on inflammation and pain 2nd symposium on NFkB Synthetic peptides as immunopharmacological tools Novel designs in clinical trials. Biosimilar pharmaceuticals Pharmacogenetics, pharmacogenomics, proteomics and phosphoproteomics Immune response in cancer First symposium on business and international cooperation on biologics Immunopharmacology 2020 is sponsored by: Cuban Society of Pharmacology (SCF) International Union of Basic and Clinical Pharmacology (IUPHAR) Latin-American Association of Pharmacology (ALF) PAHO / WHO BioCubaFarma National research centers: Finlay Vaccine Institute (IFV); Center of Genetic Engineering and Biotechnology (CIGB); Center of Molecular Immunology (CIM); Center for Control of Drugs, Equipment and Medical Devices (CECMED); National Center for Animal and Plant Health (CENSA); Tropical Medicine Institute "Pedro Kourí" (IPK); National Center for Biopreparations (BioCEN); Center for Drug Research and Development (CIDEM); Center for Clinical Trials (CENCEC); among others International Manufacturers and Companies The key objectives of the Congress are: To provide a progressive state-of-the-art report for scientists, manufacturers, governmental authorities and healthcare workers, who need to be updated about the latest scientific developments for human vaccines, including basic science, product development, market introduction, immunization programs and epidemiological surveillance. To promote the scientific collaboration among experts and institutions through the experience exchange, the presentation of results and the discussion on the conference topics. To accelerate progress in the development of vaccines and the acceptance and introduction of new methods and technologies. Opening lectures, oral presentations and posters will provide you the opportunity to be involved in a high quality congress to discuss about the progress in the field of immunology and pharmacology sciences(AU)

Estudo da biodegradabilidade de fluoroquinolona por meio da utilização de biomassas aeróbias e anaeróbias / Study of fluoroquinolone biodegradability by using aerobic and anaerobic biomass

RESUMO Os antibióticos como o norfloxacino constituem os fármacos mais utilizados na Medicina, com consumos expressivos no mundo todo. Por ser quimicamente estável, após sua administração a maior parte do fármaco é excretada de forma inalterada e, geralmente, é removida apenas parcialmente nas estações de tratamento de esgoto (ETEs). Assim, o presente trabalho buscou avaliar a eficiência dos processos biológicos na remediação de norfloxacino investigando os mecanismos de remoção envolvidos. O objetivo foi verificar a biodegradabilidade do fármaco e sua toxicidade. Para realização dos ensaios de biodegradabilidade, coletaram-se lodos na ETE Arrudas (Sabará, Minas Gerais) dos processos de tratamento com lodos ativados, reatores upflow anaerobic sludge blanket (UASB) e biodigestor anaeróbio. Reatores em escala de bancada foram montados com lodo aclimatado e não aclimatado. Amostras tiveram a biodegradabilidade acompanhada por meio da determinação do carbono orgânico total e da absortividade molar do norfloxacino por espectrofotometria de UV/Vis. Determinou-se a toxicidade por intermédio de ensaios com a bactéria Aliivibrio fischeri. Entre as biomassas utilizadas, a mais eficiente na remoção do norfloxacino foi advinda dos reatores UASB (23%), seguida do biodigestor anaeróbio (18%) e, então, dos lodos ativados (13%). Quanto à ecotoxicidade, a degradação anaeróbia promoveu a eliminação da toxicidade do antibiótico, enquanto com relação à degradação aeróbia os efluentes gerados permanecem tóxicos.

ABSTRACT Antibiotics, such as norfloxacin, are the most widely used drugs in medicine, with significant consumption in the world. By being chemically stable, most of the drug is excreted unchanged after administration, and is generally only partially removed in the sewage treatment plants (STPs). Thus, the efficiency of biological processes in the remediation of norfloxacin was investigated by the present work, verifying the removal mechanisms involved. Its objective was to verify the drug's biodegradability and toxicity. In order to perform biodegradability tests, sludges were collected in Arrudas STP (Sabara, Minas Gerais) from the treatment processes with activated sludge, upflow anaerobic sludge blanket (UASB) reactors and anaerobic biodigester. Bench-scale reactors were assembled with acclimatized and non-acclimatized sludge. Samples had their biodegradability monitored by determination of total organic carbon and norfloxacin molar absorptivity by UV/Vis spectrophotometry. The toxicity was determined by tests with Aliivibrio fischeri. Among the used biomass, UASB reactors was the most efficient in removing norfloxacin (23%), followed by anaerobic biodigester (18%), and activated sludge (13%). Regarding ecotoxicity, the anaerobic degradation promoted the elimination of antibiotic toxicity, while with aerobic degradation, the effluents generated remained toxic.

Conceptos fundamentales de bioequivalencia y biosimilitud en la normativa chilena y controversias sobre intercambiabilidad / Chilean legislation on bioequivalence and biosimilarity and current controversies related to drug interchangeability

Los medicamentos constituyen un bien económico que forma parte del gasto público y privado y de la toma de decisiones en salud. El aseguramiento de su calidad, eficacia y seguridad resulta fundamental. Sin embargo, la variada oferta disponible en el mercado chileno, donde se reconocen productos innovadores y genéricos, constituye un escenario confuso para consumidores y proveedores en salud. En esta revisión pretendemos aclarar los conceptos de fármacos bioequivalentes (aplicable a compuestos de tamaño molecular pequeño) y fármacos biosimilares (para compuestos biológicos de mayor complejidad molecular). En ambos casos, el comportamiento en el organismo del principio activo debe ser demostrado mediante estudios realizados para este fin. Una aplicación directa del concepto de bioequivalencia es la intercambiabilidad, definida como la posibilidad de utilizar un producto de un mismo principio activo, mientras la forma farmacéutica y esquema de dosificación sean iguales. Las normas relativas a esta materia y los organismos públicos encargados, no solo debieran garantizar la seguridad y la eficacia en el intercambio entre productos, sino también aspectos relacionados con el costo, la accesibilidad a los fármacos y la implementación de una guía de homogeneización de conceptos y criterios de intercambiabilidad basados en la evidencia, lo cual impactaría en una mejor educación para los usuarios, reduciendo la asimetría de información entre el usuario y la industria. La importancia de la intercambiabilidad destaca en Chile en el contexto del Plan de Garantías Explícitas en Salud (GES) y la Ley de Protección Financiera para Diagnósticos y Tratamientos de Alto Costo en Salud (Ley Ricarte Soto). Sin embargo, no es posible garantizar que todos los productos alternativos al innovador presentes en el mercado chileno son bioequivalentes. El conocimiento disponible en esta temática puede impactar y contribuir a la toma de decisiones en los prescriptores y usuarios, así como en la elaboración de políticas públicas en torno a los productos farmacéuticos bioequivalentes y biosimilares en nuestro país.

Medicines are an economic good and a fundamental component of public and private health spending and decision-making. Assurance of their quality, efficiency, and safety is essential. In Chile, the wide variety of available drugs, including innovator products, and generics­some of which are certified as bioequivalent, while others are not­creates a potentially confusing scenario for both consumers and health providers. In this review, we intend to shed light on the concepts of bioequivalency (the standard permitting interchangeability for small-molecule drugs) and biosimilarity (the standard permitting interchangeability for biological compounds of greater molecular complexity). In both cases, how the active substance interacts with the host organism must be demonstrated by studies designed and carried out for this purpose. Interchangeability is defined as the possibility of using a product of the same active principle, as long as the pharmaceutical form and dosage scheme are the same. Regulations related to bioequivalence and biosimilarity must not only guarantee safety and efficacy when products are interchanged but also facilitate cost savings and access to medicines. Implementation of evidence-based guidelines that standardize concepts of interchangeability could lead to more educated usage and reduced information asymmetry between patients (users) and industry. Drug interchangeability is particularly relevant in two government health initiatives in Chile: the Explicit Guarantees in Health Care (GES) plan, and the Law on Financial Protection for High-Cost Diagnostics and Treatment in Health Care (also known as the "Ricarte Soto Law"). Nonetheless, it is not possible to guarantee that all alternative drug products on the Chilean market are bioequivalents of the reference product. Synthesis of the available knowledge on bioequivalent and biosimilar pharmaceutical products in Chile could facilitate and contribute to stakeholder decision-making and the development of better health policies.

Survey on Timing Related to Preparation and Publishing of Risk Management Plans / 医薬品情報学

Objective: Risk Management Plan (RMP) is created and submitted by a pharmaceutical company while applying for new drug approval; it is published to be used by healthcare professionals. For example, healthcare professionals utilize RMP when considering whether to adopt a drug. However, there is no stipulation for the release date of RMPs; moreover, surveys regarding this are limited. We conducted a cross-sectional survey on the relationship between RMP-related timing and regulatory affairs-related timing.Methods: The surveyed drugs were those for which the first version of RMP was notified by PMDA Medinavi (mail delivery service) in FY2014 and FY2018. We examined regulatory affairs-related timing (i.e., “manufacturing and marketing approval date,” “drugprice standards listing date,” and “release date”) and RMP-related timing (i.e., “RMP creation date” and “Medinavi delivery date”).Results: For 7 of 43 items in FY2014 and 5 of 41 items in FY2018, the “RMP creation date” occurred later than the “drug-price standards listing date.” For one item in FY2014, the “RMP creation date” occurred later than the “release date.” For 12 items in FY2014 and 13 items in FY2018, the “Medinavi delivery date” occurred later than the “release date.”Conclusion: No considerable difference was confirmed between FY2014 and FY2018 regarding RMP-related timing and regulatory affairs timing. It was confirmed that there were several items for which the RMP creation occurred later than drug-price standard listing and items for which the publishing notice by Medinavi was delayed for drug marketing release. To promote the utilization of RMPs by healthcare professionals, RMPs must be created and published without delay.

Hollow fiber-based liquid phase microextraction followed by analytical instrumental techniques for quantitative analysis of heavy metal ions and pharmaceuticals / 药物分析学报

Hollow-fiber liquid-phase microextraction (HF-LPME) and electromembrane extraction (EME) are miniaturized extraction techniques, and have been coupled with various analytical instruments for trace analysis of heavy metals, drugs and other organic compounds, in recent years. HF-LPME and EME provide high selectivity, efficient sample cleanup and enrichment, and reduce the consumption of organic sol-vents to a few micro-liters per sample. HF-LPME and EME are compatible with different analytical in-struments for chromatography, electrophoresis, atomic spectroscopy, mass spectrometry, and electrochemical detection. HF-LPME and EME have gained significant popularity during the recent years. This review focuses on hollow fiber based techniques (especially HF-LPME and EME) of heavy metals and pharmaceuticals (published 2017 to May 2019), and their combinations with atomic spectroscopy, UV-VIS spectrophotometry, high performance liquid chromatography, gas chromatography, capillary elec-trophoresis, and voltammetry.

O que é bom para tosse? Uma perspectiva médico-sociológica sobre os remédios para tratar tosse e resfriado em pediatria / What is good for cough? A medical-sociological perspective on medicines to treat coughs and colds in pediatrics

As medicações para tosse e resfriados são amplamente conhecidos e utilizados pela população brasileira. O objetivo dessa dissertação é entender por que essas medicações são tão populares apesar das preocupações médicas a respeito do seu uso em crianças. A metodologia utilizada foi a busca de evidências científicas sobre o padrão de segurança e eficácia dessas substâncias, além do fichamento e análise de uma reunião ocorrida em 2008 pelo Food and Drugs Admnistration. Também foram utilizados autores da filosofia e sociologia para analisar os resultados encontrados como Van der Geest, Fernando Lefèvre, Philipe Pignarre e Georges Canguilhem. Os resultados obtidos indicam que essas substâncias são utilizadas pelo seu potencial sedativo em diversos casos; o estudo não encontrou evidências médicas que sustentem o uso das medicações no ponto de vista biomédico baseado em eficácia e padrão de segurança. No entanto, a análise sociológica permitiu a elaboração de que esses medicamentos assumem o papel de cuidado médico, atribuindo valores simbólicos para os processos que envolvem os quadros de resfriado e gripe. A conclusão do estudo permite afirmar que um olhar exclusivamente bioquímico sobre a substância é insuficiente se quisermos compreender o lugar social desses medicamentos, suas formas de uso e os sentidos a eles atribuídos. Os xaropes, como essa pesquisa optou por nomear genericamente essas medicações apesar do seu efeito bioquímico questionável, são capazes de exercer grande impacto nas atribuições simbólicas de doença e cura. (AU)

The medications for cough and cold are widely known and used by brazilian population. The purpose of this dissertation is to understand why these medications are so popular despite medical concerns about their use in children. The methodology used was the search for scientific evidence on safety and efficacy of these substances, in addition to the record and analysis of a meeting that took place in 2008 by the Food and Drugs Admnistration. Philosophy and sociology authors were also used to analyze the results found, such as Van der Geest, Fernando Lefèvre, Philipe Pignarre and Georges Canguilhem. The results obtained were that these substances are used due their sedative potential in several cases; the study found no medical evidence to support the use of medications in the biomedical point of view based on efficacy and safety concerns. However, the sociological analysis allowed the elaboration that these drugs assume the role of medical care, attributing symbolic values to cold and flu processes. The conclusion of the study allows us to affirm that the exclusive biochemical view of the substance is insufficient to understand the social place of these medications, their kinds of use and their meanings. Syrups, as this research chose to name these medications generically, even though they have a questionable biochemical effect, are capable of having a great impact on the symbolic attributions of disease and cure. (AU)