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[PMID]:29431542
[Au] Autor:Smit C; De Hoogd S; Brüggemann RJM; Knibbe CAJ
[Ad] Endereço:a Department of Clinical Pharmacy , St. Antonius Hospital , Nieuwegein , The Netherlands.
[Ti] Título:Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):275-285, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The rising prevalence of obesity confronts clinicians with dosing problems in the (extreme) overweight population. Obesity has a great impact on key organs that play a role in the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, however the ultimate impact of these changes on how to adapt the dose may not always be known. Areas covered: In this review, physiological changes associated with obesity are discussed. An overview is provided on the alterations in absorption, distribution, drug metabolism and clearance in (morbid) obesity focusing on general principles that can be extracted from pharmacokinetic studies. Also, relevant pharmacodynamic considerations in obesity are discussed. Expert opinion: Over the last two decades, increased knowledge is generated on PK and PD in obesity. Future research should focus on filling in the knowledge gaps that remain, especially in connecting obesity-related physiological changes with changes in PK and/or PD and vice versa. Ultimately, this knowledge can be used to develop physiologically based PK and PD models on the basis of quantitative systems pharmacology principles. Moreover, efforts should focus on thorough prospective evaluation of developed model-based doses with subsequent implementation of these dosing recommendations in clinical practice.
[Mh] Termos MeSH primário: Obesidade Mórbida/metabolismo
Obesidade/metabolismo
Preparações Farmacêuticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Seres Humanos
Modelos Biológicos
Preparações Farmacêuticas/administração & dosagem
Farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1440287


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[PMID]:29214535
[Au] Autor:Mijangos L; Ziarrusta H; Olivares M; Zuloaga O; Möder M; Etxebarria N; Prieto A
[Ad] Endereço:Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain.
[Ti] Título:Simultaneous determination of 41 multiclass organic pollutants in environmental waters by means of polyethersulfone microextraction followed by liquid chromatography-tandem mass spectrometry.
[So] Source:Anal Bioanal Chem;410(2):615-632, 2018 Jan.
[Is] ISSN:1618-2650
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A new procedure using polyethersulfone (PES) microextraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was developed in this work for the simultaneous determination of 41 multiclass priority and emerging organic pollutants including herbicides, hormones, personal care products, and pharmaceuticals, among others, in seawater, wastewater treatment plant (WWTP) effluents, and estuary samples. The optimization of the analysis included two different chromatographic columns and different variables (polarity, fragmentor voltage, collision energy, and collision cell accelerator) of the mass spectrometer. In the case of PES extraction, ion strength of the water, pH, addition of EDTA, and the amount of the polymeric material were thoroughly investigated. The developed procedure was compared with a previously validated one based on a standard solid-phase extraction (SPE). In contrast to the SPE protocol, the PES method allowed a cost-efficient extraction of complex aqueous samples with lower matrix effect from 120 mL of water sample. Satisfactory and comparable apparent recovery values (80-119 and 70-131%) and method quantification limits (MQLs, 0.4-26 and 0.2-23 ng/L) were obtained for PES and SPE procedures, respectively, regardless of the matrix. Repeatability values lower than 27% were obtained. Finally, the developed methods were applied to the analysis of real samples from the Basque Country and irbesartan, valsartan, acesulfame, and sucralose were the analytes most often detected at the highest concentrations (51-1096 ng/L). Graphical abstract Forty-one multiclass pollutant determination in environmental waters by means of PES/SPE-LC-MS/MS.
[Mh] Termos MeSH primário: Herbicidas/análise
Hormônios/análise
Preparações Farmacêuticas/análise
Polímeros/química
Extração em Fase Sólida/métodos
Sulfonas/química
Espectrometria de Massas em Tandem/métodos
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Cromatografia Líquida/métodos
Estuários
Limite de Detecção
Água do Mar/análise
Águas Residuais/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Herbicides); 0 (Hormones); 0 (Pharmaceutical Preparations); 0 (Polymers); 0 (Sulfones); 0 (Waste Water); 0 (Water Pollutants, Chemical); 25667-42-9 (polyether sulfone)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1007/s00216-017-0763-2


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[PMID]:28455844
[Au] Autor:Keshet U; Alon T; Fialkov AB; Amirav A
[Ad] Endereço:School of Chemistry, Tel Aviv University, Tel Aviv, 69978, Israel.
[Ti] Título:Open Probe fast GC-MS - combining ambient sampling ultra-fast separation and in-vacuum ionization for real-time analysis.
[So] Source:J Mass Spectrom;52(7):417-426, 2017 Jul.
[Is] ISSN:1096-9888
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An Open Probe inlet was combined with a low thermal mass ultra-fast gas chromatograph (GC), in-vacuum electron ionization ion source and a mass spectrometer (MS) of GC-MS for obtaining real-time analysis with separation. The Open Probe enables ambient sampling via sample vaporization in an oven that is open to room air, and the ultra-fast GC provides ~30-s separation, while if no separation is required, it can act as a transfer line with 2 to 3-s sample transfer time. Sample analysis is as simple as touching the sample, pushing the sample holder into the Open Probe oven and obtaining the results in 30 s. The Open Probe fast GC was mounted on a standard Agilent 7890 GC that was coupled with an Agilent 5977A MS. Open Probe fast GC-MS provides real-time analysis combined with GC separation and library identification, and it uses the low-cost MS of GC-MS. The operation of Open Probe fast GC-MS is demonstrated in the 30-s separation and 50-s full analysis cycle time of tetrahydrocannabinol and cannabinol in Cannabis flower, sub 1-min analysis of trace trinitrotoluene transferred from a finger onto a glass surface, vitamin E in canola oil, sterols in olive oil, polybrominated flame retardants in plastics, alprazolam in Xanax drug pill and free fatty acids and cholesterol in human blood. The extrapolated limit of detection for pyrene is <1 fg, but the concentration is too high and the software noise calculation is untrustworthy. The broad range of compounds amenable for analysis is demonstrated in the analysis of reserpine. The possible use with alternate standard GC-MS and Open Probe fast GC-MS is demonstrated in the analysis of heroin in its street drug powder. The use of Open Probe with the fast GC acting as a transfer line is demonstrated in <10-s analysis without separation of ibuprofen and estradiol. Copyright © 2017 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Cromatografia Gasosa-Espectrometria de Massas/instrumentação
Cromatografia Gasosa-Espectrometria de Massas/métodos
Compostos Orgânicos/análise
[Mh] Termos MeSH secundário: Ionização do Ar
Seres Humanos
Limite de Detecção
Preparações Farmacêuticas/análise
Preparações Farmacêuticas/química
Drogas Ilícitas/análise
Drogas Ilícitas/química
Vácuo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Chemicals); 0 (Pharmaceutical Preparations); 0 (Street Drugs)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1002/jms.3941


  4 / 45334 MEDLINE  
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[PMID]:29295698
[Au] Autor:Usha T; Shanmugarajan D; Goyal AK; Kumar CS; Middha SK
[Ad] Endereço:Department of Biochemistry, Bangalore University, Bengaluru, Karnataka, India.
[Ti] Título:Recent Updates on Computer-aided Drug Discovery: Time for a Paradigm Shift.
[So] Source:Curr Top Med Chem;17(30):3296-3307, 2017.
[Is] ISSN:1873-4294
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Computer-Aided Drug Designing (CADD) has gained a wide popularity among biologists and chemists as a part of interdisciplinary drug discovery approach. It plays a vital role in the discovery, design and analysis of drugs in pharmaceutical industry. It is extensively used to reduce cost, time and speed up the early stage development of biologically new active molecules. In the current review we presented a brief review of CADD, merits and demerits, DNA, protein and enzyme as targets, types of CADD: Structure Based Drug Designing (SBDD), Ligand Based Drug Designing (LBDD), Pharmacophore based drug designing (PBDD) and Fragment Based Drug Designing (FBDD), theory behind the types of CADD and their applications. The review also focuses on the in-silico pharmokinetic, pharmacodynamic and toxicity filters or predictions that play a major role in identifying the drug like molecules. Currently in pharmaceutical sciences computational tools and software are exhibiting imperative role in the different stages of drug discovery hence the review throws light on various commercial and freeware available for each step of CADD.
[Mh] Termos MeSH primário: Projeto Auxiliado por Computador
Descoberta de Drogas/métodos
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Preparações Farmacêuticas/metabolismo
Software
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.2174/1568026618666180101163651


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[PMID]:28968945
[Au] Autor:Amorim CL; Alves M; Castro PML; Henriques I
[Ad] Endereço:Biology Department and CESAM, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; Universidade Católica Portuguesa, CBQF - Centro de Biotecnologia e Química Fina, Laboratório Associado, Escola Superior de Biotecnologia, Rua Arquiteto Lobão Vital 172, 4200-374 Porto, Po
[Ti] Título:Bacterial community dynamics within an aerobic granular sludge reactor treating wastewater loaded with pharmaceuticals.
[So] Source:Ecotoxicol Environ Saf;147:905-912, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Pharmaceuticals are micropollutants often present in wastewater treatment systems. In this study, the potential impact of such micropollutants on the bacterial population within aerobic granular sludge (AGS) bioreactor was investigated. The AGS bacterial community structure and composition were accessed combining DGGE fingerprinting and barcoded pyrosequencing analysis. Both revealed the existence of a dynamic bacterial community, independently of the pharmaceuticals presence. The AGS microbiome at both phylum and class levels varied over time and, after stopping pharmaceuticals feeding, the bacterial community did not return to its initial composition. Nevertheless, most of the assigned OTUs were present throughout the different operational phases. This core microbiome, represented by over 72% of the total sequences in each phase, probably played an important role in biological removal processes, avoiding their failure during the disturbance period. Quantitative-PCR revealed that pharmaceuticals load led to gradual changes on the abundance of ammonia-oxidizing bacteria (AOB), nitrite-oxidizing bacteria (NOB) and polyphosphate-accumulating organisms (PAO) but their persistence during that phase demonstrated the resilience of such bacterial groups. AGS microbiome changed over time but a core community was maintained, probably ensuring the accomplishment of the main biological removal processes.
[Mh] Termos MeSH primário: Reatores Biológicos/microbiologia
Microbiota/efeitos dos fármacos
Preparações Farmacêuticas/análise
Esgotos/microbiologia
Águas Residuais/microbiologia
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Aerobiose
Microbiota/genética
RNA Ribossômico 16S/genética
Esgotos/química
Águas Residuais/química
Purificação da Água/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pharmaceutical Preparations); 0 (RNA, Ribosomal, 16S); 0 (Sewage); 0 (Waste Water); 0 (Water Pollutants, Chemical)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE


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[PMID]:28463419
[Au] Autor:Lin C; Khetani SR
[Ad] Endereço:School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado.
[Ti] Título:Micropatterned Co-Cultures of Human Hepatocytes and Stromal Cells for the Assessment of Drug Clearance and Drug-Drug Interactions.
[So] Source:Curr Protoc Toxicol;72:14.17.1-14.17.23, 2017 May 02.
[Is] ISSN:1934-9262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Drug clearance rates from the body can determine drug exposure that can affect efficacy or toxicity. Thus, accurate prediction of drug clearance during preclinical development can help guide dose selection in humans, but animal testing is not always predictive of human outcomes. Because hepatic drug metabolism is a rate-limiting step in the overall clearance of many drugs, primary human hepatocytes (PHHs) in suspension cultures or monolayers are used for drug clearance predictions. Yet, the precipitous decline in drug metabolism capacity can lead to significant underestimation of clearance rates, particularly for low turnover compounds that have desirable one-pill-a-day dosing regimens. In contrast, micropatterned co-cultures (MPCCs) of PHHs and fibroblasts display phenotypic stability for several weeks and can help mitigate the limitations of conventional cultures. Here, we describe protocols to create and use MPCCs for drug clearance predictions, and for modeling clinically-relevant drug-drug interactions that can affect drug clearance. © 2017 by John Wiley & Sons, Inc.
[Mh] Termos MeSH primário: Técnicas de Cocultura/métodos
Interações Medicamentosas
Hepatócitos/metabolismo
Preparações Farmacêuticas/metabolismo
Células Estromais/metabolismo
[Mh] Termos MeSH secundário: Células 3T3
Animais
Técnicas de Cultura de Células
Meios de Cultura
Fibroblastos/metabolismo
Hepatócitos/ultraestrutura
Seres Humanos
Taxa de Depuração Metabólica
Camundongos
Fenótipo
Células Estromais/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/cptx.23


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[PMID]:29311542
[Au] Autor:Cao J; Perez-Pinera P; Lowenhaupt K; Wu MR; Purcell O; de la Fuente-Nunez C; Lu TK
[Ad] Endereço:Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
[Ti] Título:Versatile and on-demand biologics co-production in yeast.
[So] Source:Nat Commun;9(1):77, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.
[Mh] Termos MeSH primário: Produtos Biológicos/metabolismo
Preparações Farmacêuticas/metabolismo
Saccharomyces cerevisiae/metabolismo
Tecnologia Farmacêutica/métodos
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/biossíntese
Anticorpos Monoclonais/isolamento & purificação
Produtos Biológicos/isolamento & purificação
Análise Custo-Benefício
Seres Humanos
Preparações Farmacêuticas/isolamento & purificação
Saccharomyces cerevisiae/crescimento & desenvolvimento
Tecnologia Farmacêutica/economia
Tecnologia Farmacêutica/instrumentação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Biological Products); 0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02587-w


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[PMID]:29293194
[Au] Autor:Eisenberg S
[Ad] Endereço:Seattle Cancer Care Alliance, Ambulatory Clinic, Seattle, Washington. Seth Eisenberg, ADN, RN, OCN®, BMTCN®, is a professional practice coordinator for infusion services at the Seattle Cancer Care Alliance, Ambulatory Clinic, in Seattle, Washington. He has practiced in the field of oncology since 1983. His experience includes 32 years in hematopoietic stem cell transplantation. He specializes in hazardous drug safety and has published numerous articles and book chapters on chemotherapy and biotherapy.
[Ti] Título:USP <800> and Strategies to Promote Hazardous Drug Safety.
[So] Source:J Infus Nurs;41(1):12-23, 2018 Jan/Feb.
[Is] ISSN:1539-0667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The term hazardous drug (HD) includes medications that have any of the following properties: carcinogenicity, teratogenicity, reproductive toxicities, genotoxicities, toxicities at low doses, and a structure that mimics other drugs meeting the criteria. Numerous studies continue to demonstrate widespread environmental contamination and human uptake of these agents. Safe handling guidelines have existed for more than 30 years but have not been routinely implemented. USP General Chapter 800 (USP <800>) represents a new enforceable standard for HD safety. Nurses will need to understand the impact of USP <800>, which is expected to be enforced beginning December 1, 2019.
[Mh] Termos MeSH primário: Substâncias Perigosas/normas
Exposição Ocupacional/prevenção & controle
Guias de Prática Clínica como Assunto/normas
Gestão da Segurança/normas
[Mh] Termos MeSH secundário: Antineoplásicos/administração & dosagem
Antineoplásicos/toxicidade
Substâncias Perigosas/toxicidade
Seres Humanos
Recursos Humanos de Enfermagem no Hospital/normas
Preparações Farmacêuticas
Roupa de Proteção
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Hazardous Substances); 0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:N
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1097/NAN.0000000000000257


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[PMID]:29406689
[Ti] Título:Send in the (Potentially Life-Saving) Drones.
[So] Source:J AHIMA;88(2):64, 2017 02.
[Is] ISSN:1060-5487
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Aeronaves
Acesso aos Serviços de Saúde
Preparações Farmacêuticas
[Mh] Termos MeSH secundário: Seres Humanos
Áreas de Pobreza
Privacidade
População Rural
Virginia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:H
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


  10 / 45334 MEDLINE  
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[PMID]:29386431
[Au] Autor:Ohashi Y
[Ad] Endereço:Quality & Regulatory Compliance Unit, Chugai Pharmaceutical Co., Ltd.
[Ti] Título:[Safe Use of Recent New Drugs-Current Status and Challenges].
[So] Source:Yakugaku Zasshi;138(2):177-183, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: In Japan and overseas, Chugai Pharmaceutical Company handles numerous biopharmaceuticals, molecular targeted therapies and other pharmaceuticals with innovative modes of action. Expert safety evaluation is essential for promoting the appropriate use of these pharmaceuticals around the world and in gaining acceptance from patients and healthcare professionals (HCPs), while speedy decision-making is crucial for the timely collection and provision of safety information and thus ensuring safety. In 2015, we collected safety information on more than 180000 cases and evaluated it from a medical standpoint. We have established a system for recording the collected information in a global database, and are conducting signal detection of adverse drug reactions using this database. With this system, we promptly disclose information to regulatory authorities in Japan, the US, Europe and Asia. We have in-house medical doctors with abundant clinical experience who conduct expert safety evaluations. Many innovative drugs, such as anticancer drugs or biopharmaceuticals, require wider-ranging, more rigorous management, including the provision of appropriate safety information to HCPs, management of distribution through wholesalers and dispensing pharmacies, and confirmation of conditions of use, in addition to all-case registration surveillance. With progress in the development of individualized medicine and drugs with new modes of action, in order for HCPs to understand the characteristics of these new drugs and use them appropriately, pharmacists and pharmaceutical companies should cooperate in promoting their appropriate use in the spirit of 'All Pharmacists for Patients'.
[Mh] Termos MeSH primário: Bases de Dados de Produtos Farmacêuticos
Serviços de Informação sobre Medicamentos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Preparações Farmacêuticas
Farmacovigilância
Gestão de Riscos
[Mh] Termos MeSH secundário: Biofarmácia
Tomada de Decisões Gerenciais
Indústria Farmacêutica
Seres Humanos
Farmacêuticos
Medicina de Precisão/tendências
Segurança
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pharmaceutical Preparations)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00174-3



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