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[PMID]:29318278
[Au] Autor:Atri A; Frölich L; Ballard C; Tariot PN; Molinuevo JL; Boneva N; Windfeld K; Raket LL; Cummings JL
[Ad] Endereço:Ray Dolby Brain Health Center, California Pacific Medical Center, San Francisco.
[Ti] Título:Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.
[So] Source:JAMA;319(2):130-142, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: New therapeutic approaches for Alzheimer disease (AD) are needed. Objective: To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Design, Setting, and Participants: Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Interventions: Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Main Outcomes and Measures: Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Results: Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0.53 for the 10-mg dose group, and 0.56 for the placebo group (adjusted mean difference vs placebo, 0.63 [95% CI, -0.38 to 1.65] for the 30-mg dose group; given the gated testing strategy and the null findings at the 30-mg dose, statistical comparison of the 10-mg dose was not performed). In study 3, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.38 for the 60-mg dose of idalopirdine group and 0.82 for the placebo group (adjusted mean difference vs placebo, -0.55 [95% CI, -1.45 to 0.36]). Treatment-emergent adverse events occurred in between 55.4% and 69.7% of participants in the idalopirdine groups vs between 56.7% and 61.4% of participants in the placebo groups. Conclusions and Relevance: In patients with mild to moderate AD, the use of idalopirdine compared with placebo did not improve cognition over 24 weeks of treatment. These findings do not support the use of idalopirdine for the treatment of AD. Trial Registration: clinicaltrials.gov Identifiers: NCT01955161, NCT02006641, and NCT02006654.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Benzilaminas/uso terapêutico
Inibidores da Colinesterase/uso terapêutico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Acidentes por Quedas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Benzilaminas/administração & dosagem
Benzilaminas/efeitos adversos
Inibidores da Colinesterase/efeitos adversos
Cognição/efeitos dos fármacos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indóis/administração & dosagem
Indóis/efeitos adversos
Masculino
Meia-Idade
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Indoles); 0 (Piperidines); 0 (Serotonin Antagonists); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20373


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[PMID]:28460083
[Au] Autor:Rendas-Baum R; Kosinski M; Singh A; Mebus CA; Wilkinson BE; Wallenstein GV
[Ad] Endereço:QualityMetric Incorporated Lincoln, RI.
[Ti] Título:Estimated medical expenditure and risk of job loss among rheumatoid arthritis patients undergoing tofacitinib treatment: post hoc analyses of two randomized clinical trials.
[So] Source:Rheumatology (Oxford);56(8):1386-1394, 2017 Aug 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Methods: Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. Results: MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P < 0.001); >20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾16%, and risk of future job loss decreased ∼20% (P < 0.001 vs placebo). MME reduction by month 3 was $70 greater for tofacitinib- than placebo-treated MTX inadequate responders (P < 0.001); ⩾23 and 13% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾31% and risk of future job loss decreased ⩾25% (P < 0.001 vs placebo). Conclusion: Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi.
[Mh] Termos MeSH primário: Antirreumáticos/economia
Artrite Reumatoide/economia
Efeitos Psicossociais da Doença
Gastos em Saúde
Piperidinas/economia
Pirimidinas/economia
Pirróis/economia
Retorno ao Trabalho/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adalimumab/administração & dosagem
Adalimumab/economia
Adulto
Antirreumáticos/administração & dosagem
Artrite Reumatoide/tratamento farmacológico
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seres Humanos
Masculino
Metotrexato/administração & dosagem
Metotrexato/economia
Meia-Idade
Piperidinas/administração & dosagem
Pirimidinas/administração & dosagem
Pirróis/administração & dosagem
Fatores de Risco
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antirheumatic Agents); 0 (Piperidines); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib); FYS6T7F842 (Adalimumab); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex087


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[PMID]:29318298
[Au] Autor:Jukic M; Grabrijan K; Kadic S; Lera Garrido FJ; Sosic I; Gobec S; Obreza A
[Ti] Título:Chlorocarbonylsulfenyl Chloride Cyclizations Towards Piperidin-3-yl-oxathiazol-2-ones as Potential Covalent Inhibitors of Threonine Proteases.
[So] Source:Acta Chim Slov;64(4):771-781, 2017 Dec.
[Is] ISSN:1318-0207
[Cp] País de publicação:Slovenia
[La] Idioma:eng
[Ab] Resumo:Using rescaffolding approach, we designed piperidine compounds decorated with an electrophilic oxathiazol-2-one moiety that is known to confer selectivity towards threonine proteases. Our efforts to prepare products according to the published procedures were not successful. Furthermore we identified major side products containing nitrile functional group, resulting from carboxamide dehydration. We systematically optimized reaction conditions towards our desired products to identify heating of carboxamides with chlorocarbonylsulfenyl chloride and sodium carbonate as base in dioxane at 100 °C. Our efforts culminated in the preparation of a small series of piperidin-3-yl-oxathiazol-2-ones that are suitable for further biological evaluation.
[Mh] Termos MeSH primário: Piperidinas/química
Inibidores de Proteases/síntese química
Tiazóis/química
Treonina/metabolismo
[Mh] Termos MeSH secundário: Ciclização
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Piperidines); 0 (Protease Inhibitors); 0 (Thiazoles); 2ZD004190S (Threonine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE


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[PMID]:28741230
[Au] Autor:Velayudhan L; Ffytche D; Ballard C; Aarsland D
[Ad] Endereço:Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neurosciences, Kings College London, Box PO 70, De Crespigny Park, London, SE5 8AF, UK.
[Ti] Título:New Therapeutic Strategies for Lewy Body Dementias.
[So] Source:Curr Neurol Neurosci Rep;17(9):68, 2017 Sep.
[Is] ISSN:1534-6293
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This article reviews current treatment strategies and recent advances for the Lewy body dementias (LBDs). Current available symptom treatment strategies are based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems. Relatively robust evidence exists for cholinesterase inhibitors for cognitive impairment in LBD and in Parkinson's disease for antidepressants, clozapine and recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are currently under investigation. Non-pharmacological interventions, such as cognitive stimulation, physical exercises and neuromodulation strategies, may be useful in Parkinson's disease but have not yet been tested in dementias. Disease-modifying approaches are aimed at preventing, slowing or ameliorating the production, aggregation and deposition of pathological proteins, including immunotherapy targeting α-synuclein and an ongoing trial using ambroxol which increases glucocerebrosidase activity to lower the levels of the protein alpha-synuclein. Other disease-modifying clinical trials are using agents to augment insulin signalling, stem cell therapy, reducing amyloid pathology and gene therapy.
[Mh] Termos MeSH primário: Gerenciamento Clínico
Doença por Corpos de Lewy/diagnóstico
Doença por Corpos de Lewy/terapia
[Mh] Termos MeSH secundário: Inibidores da Colinesterase/uso terapêutico
Terapia Genética/tendências
Seres Humanos
Doença por Corpos de Lewy/imunologia
Doença de Parkinson/diagnóstico
Doença de Parkinson/imunologia
Doença de Parkinson/terapia
Piperidinas/uso terapêutico
Transplante de Células-Tronco/tendências
Ureia/análogos & derivados
Ureia/uso terapêutico
alfa-Sinucleína/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Piperidines); 0 (alpha-Synuclein); 8W8T17847W (Urea); JZ963P0DIK (pimavanserin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1007/s11910-017-0778-2


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[PMID]:29335209
[Au] Autor:Chierrito TPC; Pedersoli-Mantoani S; Roca C; Sebastian-Pérez V; Martínez-Gonzalez L; Pérez DI; Perez C; Canales A; Cañada FJ; Campillo NE; Carvalho I; Martinez A
[Ad] Endereço:Centro de Investigaciones Biologicas (CIB-CSIC), Ramiro de Maetzu 9, Madrid, Spain; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/ n, 14040-903, Ribeirão Preto, SP, Brazil.
[Ti] Título:Chameleon-like behavior of indolylpiperidines in complex with cholinesterases targets: Potent butyrylcholinesterase inhibitors.
[So] Source:Eur J Med Chem;145:431-444, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Alzheimer's disease (AD) is the most common form of dementia worldwide with an increasing prevalence for the next years. The multifactorial nature of AD precludes the design of new drugs directed to a single target being probably one of the reasons for recent failures. Therefore, dual binding site acetylcholinesterase (AChE) inhibitors have been revealed as cognitive enhancers and ß-amyloid modulators offering an alternative in AD therapy field. Based on the dual ligands NP61 and donepezil, the present study reports the synthesis of a series of indolylpiperidines hybrids to optimize the NP61 structure preserving the indole nucleus, but replacing the tacrine moiety of NP61 by benzyl piperidine core found in donepezil. Surprisingly, this new family of indolylpiperidines derivatives showed very potent and selective hBuChE inhibition. Further studies of NMR and molecular dynamics have showed the capacity of these hybrid molecules to change their bioactive conformation depending on the binding site, being capable to inhibit with different shapes BuChE and residually AChE.
[Mh] Termos MeSH primário: Acetilcolinesterase/metabolismo
Butirilcolinesterase/metabolismo
Inibidores da Colinesterase/farmacologia
Indóis/farmacologia
Piperidinas/farmacologia
[Mh] Termos MeSH secundário: Inibidores da Colinesterase/síntese química
Inibidores da Colinesterase/química
Relação Dose-Resposta a Droga
Seres Humanos
Indóis/síntese química
Indóis/química
Estrutura Molecular
Piperidinas/síntese química
Piperidinas/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Indoles); 0 (Indolylpiperidine); 0 (Piperidines); EC 3.1.1.7 (Acetylcholinesterase); EC 3.1.1.8 (Butyrylcholinesterase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:29289886
[Au] Autor:Li HY; Lee JD; Chen CW; Sun YC; Cheng WC
[Ad] Endereço:Genomics Research Center, Academia Sinica, 128, Academia Road, Section 2, Nankang, Taipei 115, Taiwan; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155, Linong Street, Section 2, Taipei 112, Taiwan.
[Ti] Título:Synthesis of (3S,4S,5S)-trihydroxylpiperidine derivatives as enzyme stabilizers to improve therapeutic enzyme activity in Fabry patient cell lines.
[So] Source:Eur J Med Chem;144:626-634, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of 3S,4S,5S-trihydroxylated piperidines bearing structural diversity at C-2 or C-6 positions has been synthesized and tested to determine their ability to stabilize the activity of recombinant human α-Galactosidase A (rh-α-Gal A). Hit molecules were identified by rapid inhibitory activity screening, and then further investigated for their ability to protect this enzyme from thermo-induced denaturation and enhance its activity in Fabry patient cell lines. Our study resulted in the identification of a new class of small molecules as enzyme stabilizers for the potential treatment of Fabry disease. Of these, stabilizer 21 was the most effective, showing a 12-fold increase in rh-α-Gal A activity in Fabry disease cell lines.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/farmacologia
Doença de Fabry/tratamento farmacológico
Piperidinas/farmacologia
alfa-Galactosidase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Linhagem Celular
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Estabilidade Enzimática
Doença de Fabry/metabolismo
Doença de Fabry/patologia
Seres Humanos
Estrutura Molecular
Piperidinas/síntese química
Piperidinas/química
Proteínas Recombinantes/metabolismo
Relação Estrutura-Atividade
alfa-Galactosidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Piperidines); 0 (Recombinant Proteins); EC 3.2.1.22 (alpha-Galactosidase); EC 3.2.1.22 (alpha-galactosidase A, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


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[PMID]:29469555
[Au] Autor:Aletaha D; Kerschbaumer A; Smolen JS
[Ad] Endereço:Medical University of Vienna, Vienna, Austria
[Ti] Título:Tofacitinib for Psoriatic Arthritis.
[So] Source:N Engl J Med;378(8):775, 2018 02 22.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Artrite Psoriásica
Pirimidinas
[Mh] Termos MeSH secundário: Piperidinas
Pirróis
[Pt] Tipo de publicação:LETTER; COMMENT
[Nm] Nome de substância:
0 (Piperidines); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180223
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMc1715189


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[PMID]:29466165
[Au] Autor:Mease P; Gladman D
[Ad] Endereço:Swedish Medical Center, Seattle, WA pmease@philipmease.com
[Ti] Título:Tofacitinib for Psoriatic Arthritis.
[So] Source:N Engl J Med;378(8):775-776, 2018 02 22.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Artrite Psoriásica
Pirimidinas
[Mh] Termos MeSH secundário: Antirreumáticos
Artrite Reumatoide
Seres Humanos
Piperidinas
Inibidores de Proteínas Quinases
Pirróis
Resultado do Tratamento
[Pt] Tipo de publicação:LETTER; COMMENT
[Nm] Nome de substância:
0 (Antirheumatic Agents); 0 (Piperidines); 0 (Protein Kinase Inhibitors); 0 (Pyrimidines); 0 (Pyrroles); 87LA6FU830 (tofacitinib)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMc1715189


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[PMID]:29386436
[Au] Autor:Komada F
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Himeji Dokkyo University.
[Ti] Título:[Analysis of Time-to-onset of Interstitial Lung Disease after the Administration of Small Molecule Molecularly-targeted Drugs].
[So] Source:Yakugaku Zasshi;138(2):229-235, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo: The aim of this study was to investigate the time-to-onset of drug-induced interstitial lung disease (DILD) following the administration of small molecule molecularly-targeted drugs via the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for afatinib, alectinib, bortezomib, crizotinib, dasatinib, erlotinib, everolimus, gefitinib, imatinib, lapatinib, nilotinib, osimertinib, sorafenib, sunitinib, temsirolimus, and tofacitinib were used to calculate the median onset times of DILD and the Weibull distribution parameters, and to perform the hierarchical cluster analysis. The median onset times of DILD for afatinib, bortezomib, crizotinib, erlotinib, gefitinib, and nilotinib were within one month. The median onset times of DILD for dasatinib, everolimus, lapatinib, osimertinib, and temsirolimus ranged from 1 to 2 months. The median onset times of the DILD for alectinib, imatinib, and tofacitinib ranged from 2 to 3 months. The median onset times of the DILD for sunitinib and sorafenib ranged from 8 to 9 months. Weibull distributions for these drugs when using the cluster analysis showed that there were 4 clusters. Cluster 1 described a subgroup with early to later onset DILD and early failure type profiles or a random failure type profile. Cluster 2 exhibited early failure type profiles or a random failure type profile with early onset DILD. Cluster 3 exhibited a random failure type profile or wear out failure type profiles with later onset DILD. Cluster 4 exhibited an early failure type profile or a random failure type profile with the latest onset DILD.
[Mh] Termos MeSH primário: Sistemas de Notificação de Reações Adversas a Medicamentos
Bortezomib/efeitos adversos
Carbazóis/efeitos adversos
Bases de Dados como Assunto
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia
Doenças Pulmonares Intersticiais/induzido quimicamente
Piperidinas/efeitos adversos
Quinazolinas/efeitos adversos
[Mh] Termos MeSH secundário: Análise por Conglomerados
Dasatinibe/efeitos adversos
Conjuntos de Dados como Assunto
Seres Humanos
Japão/epidemiologia
Doenças Pulmonares Intersticiais/epidemiologia
Terapia de Alvo Molecular/efeitos adversos
Tamanho da Partícula
Pirazóis/efeitos adversos
Piridinas/efeitos adversos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CH5424802); 0 (Carbazoles); 0 (Piperidines); 0 (Pyrazoles); 0 (Pyridines); 0 (Quinazolines); 41UD74L59M (afatinib); 53AH36668S (crizotinib); 69G8BD63PP (Bortezomib); RBZ1571X5H (Dasatinib)
[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.17-00194


  10 / 31928 MEDLINE  
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[PMID]:29441996
[Au] Autor:Ayoub BM; Abdel-Aziz O
[Ti] Título:A guide for using experimental design in chromatographic method development: applied to the analysis of selected anti-diabetic pharmaceutical combinations.
[So] Source:Pharmazie;71(12):683-690, 2016 Dec 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A guide experimental design in chromatographic method development was described and applied successfully to the analysis of different recently approved anti-diabetic pharmaceutical combinations. Enhancement of UHPLC analysis of alogliptin benzoate either with pioglitazone hydrochloride or with metformin hydrochloride was achieved. The optimal chromatographic conditions were not attained by trial and error that requires a large number of experiments. Alternatively, a computer program was used as a systematic optimization strategy for the design of the experiment which accurately predicts the combined effect of different factors simultaneously. Resolution between peaks was studied by the proposed fractional factorial design approach performed by the Minitab® Program using screening and optimization steps. Application of the central composite design was implemented. A Pareto chart was used to exclude the insignificant variables. Linearity ranges were found to be 0.5-40 µg ml-1, 1-20 µg ml-1 and 1-32 µg ml-1 for alogliptin benzoate, pioglitazone hydrochloride and metformin hydrochloride, respectively. The proposed method is applicable for the analysis of six pharmaceutical dosage forms namely, Nesina®, Actos®, Glucophage®, Oseni®, Kazano® and Actoplus MET® tablets.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Hipoglicemiantes/análise
[Mh] Termos MeSH secundário: Formas de Dosagem
Combinação de Medicamentos
Desenho de Equipamento
Metformina/análise
Piperidinas/análise
Padrões de Referência
Reprodutibilidade dos Testes
Soluções
Comprimidos/análise
Tiazolidinedionas/análise
Uracila/análogos & derivados
Uracila/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dosage Forms); 0 (Drug Combinations); 0 (Hypoglycemic Agents); 0 (Piperidines); 0 (Solutions); 0 (Tablets); 0 (Thiazolidinediones); 56HH86ZVCT (Uracil); 9100L32L2N (Metformin); JHC049LO86 (alogliptin); X4OV71U42S (pioglitazone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6095



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