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[PMID]:27773524
[Au] Autor:Viciosa MT; Moura Ramos JJ; Diogo HP
[Ad] Endereço:Centro de Química-Física Molecular and Institute of Nanoscience and Nanotechnology, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
[Ti] Título:The Slow Relaxation Dynamics in the Amorphous Pharmaceutical Drugs Cimetidine, Nizatidine, and Famotidine.
[So] Source:J Pharm Sci;105(12):3573-3584, 2016 Dec.
[Is] ISSN:1520-6017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The slow molecular mobility in the amorphous solid state of 3 active pharmaceutical drugs (cimetidine, nizatidine, and famotidine) has been studied using differential scanning calorimetry and the 2 dielectric-related techniques of dielectric relaxation spectroscopy and thermally stimulated depolarization currents. The glass-forming ability, the glass stability, and the tendency for crystallization from the equilibrium melt were investigated by differential scanning calorimetry, which also provided the characterization of the main relaxation of the 3 glass formers. The chemical instability of famotidine at the melting temperature and above it prevented the preparation of the amorphous for dielectric studies. In contrast, for cimetidine and nizatidine, the dielectric study yielded the main kinetic features of the α relaxation and of the secondary relaxations. According to the obtained results, nizatidine displays the higher fragility index of the 3 studied glass-forming drugs. The thermally stimulated depolarization current technique has proved useful to identify the Johari-Goldstein relaxation and to measure τ in the amorphous solid state, that is, in a frequency range which is not easily accessible by dielectric relaxation spectroscopy.
[Mh] Termos MeSH primário: Química Farmacêutica/métodos
Cimetidina/química
Famotidina/química
Nizatidina/química
[Mh] Termos MeSH secundário: Varredura Diferencial de Calorimetria/métodos
Cimetidina/metabolismo
Famotidina/metabolismo
Nizatidina/metabolismo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5QZO15J2Z8 (Famotidine); 80061L1WGD (Cimetidine); P41PML4GHR (Nizatidine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28513067
[Au] Autor:van der Wouden JC; van der Sande R; Kruithof EJ; Sollie A; van Suijlekom-Smit LW; Koning S
[Ad] Endereço:Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, VU University Medical Center, PO Box 7057, Amsterdam, Netherlands, 1007 MB.
[Ti] Título:Interventions for cutaneous molluscum contagiosum.
[So] Source:Cochrane Database Syst Rev;5:CD004767, 2017 05 17.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Molluscum contagiosum is a common skin infection that is caused by a pox virus and occurs mainly in children. The infection usually resolves within months in people without immune deficiency, but treatment may be preferred for social and cosmetic reasons or to avoid spreading the infection. A clear evidence base supporting the various treatments is lacking.This is an update of a Cochrane Review first published in 2006, and updated previously in 2009. OBJECTIVES: To assess the effects of specific treatments and management strategies, including waiting for natural resolution, for cutaneous, non-genital molluscum contagiosum in people without immune deficiency. SEARCH METHODS: We updated our searches of the following databases to July 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched six trial registers and checked the reference lists of included studies and review articles for further references to relevant randomised controlled trials. We contacted pharmaceutical companies and experts in the field to identify further relevant randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials of any treatment of molluscum contagiosum in people without immune deficiency. We excluded trials on sexually transmitted molluscum contagiosum and in people with immune deficiency (including those with HIV infection). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We obtained missing data from study authors where possible. MAIN RESULTS: We found 11 new studies for this update, resulting in 22 included studies with a total of 1650 participants. The studies examined the effects of topical (20 studies) and systemic interventions (2 studies).Among the new included studies were the full trial reports of three large unpublished studies, brought to our attention by an expert in the field. They all provided moderate-quality evidence for a lack of effect of 5% imiquimod compared to vehicle (placebo) on short-term clinical cure (4 studies, 850 participants, 12 weeks after start of treatment, risk ratio (RR) 1.33, 95% confidence interval (CI) 0.92 to 1.93), medium-term clinical cure (2 studies, 702 participants, 18 weeks after start of treatment, RR 0.88, 95% CI 0.67 to 1.14), and long-term clinical cure (2 studies, 702 participants, 28 weeks after start of treatment, RR 0.97, 95% CI 0.79 to 1.17). We found similar but more certain results for short-term improvement (4 studies, 850 participants, 12 weeks after start of treatment, RR 1.14, 95% CI 0.89 to 1.47; high-quality evidence). For the outcome 'any adverse effect', we found high-quality evidence for little or no difference between topical 5% imiquimod and vehicle (3 studies, 827 participants, RR 0.97, 95% CI 0.88 to 1.07), but application site reactions were more frequent in the groups treated with imiquimod (moderate-quality evidence): any application site reaction (3 studies, 827 participants, RR 1.41, 95% CI 1.13 to 1.77, the number needed to treat for an additional harmful outcome (NNTH) was 11); severe application site reaction (3 studies, 827 participants, RR 4.33, 95% CI 1.16 to 16.19, NNTH over 40).For the following 11 comparisons, there was limited evidence to show which treatment was superior in achieving short-term clinical cure (low-quality evidence): 5% imiquimod less effective than cryospray (1 study, 74 participants, RR 0.60, 95% CI 0.46 to 0.78) and 10% potassium hydroxide (2 studies, 67 participants, RR 0.65, 95% CI 0.46 to 0.93); 10% Australian lemon myrtle oil more effective than olive oil (1 study, 31 participants, RR 17.88, 95% CI 1.13 to 282.72); 10% benzoyl peroxide cream more effective than 0.05% tretinoin (1 study, 30 participants, RR 2.20, 95% CI 1.01 to 4.79); 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5% salicylic acid alone (1 study, 30 participants, RR 3.50, 95% CI 1.23 to 9.92); and iodine plus tea tree oil more effective than tea tree oil (1 study, 37 participants, RR 0.20, 95% CI 0.07 to 0.57) or iodine alone (1 study, 37 participants, RR 0.07, 95% CI 0.01 to 0.50). Although there is some uncertainty, 10% potassium hydroxide appears to be more effective than saline (1 study, 20 participants, RR 3.50, 95% CI 0.95 to 12.90); homeopathic calcarea carbonica appears to be more effective than placebo (1 study, 20 participants, RR 5.57, 95% CI 0.93 to 33.54); 2.5% appears to be less effective than 5% solution of potassium hydroxide (1 study, 25 participants, RR 0.35, 95% CI 0.12 to 1.01); and 10% povidone iodine solution plus 50% salicylic acid plaster appears to be more effective than salicylic acid plaster alone (1 study, 30 participants, RR 1.43, 95% CI 0.95 to 2.16).We found no statistically significant differences for other comparisons (most of which addressed two different topical treatments). We found no randomised controlled trial evidence for expressing lesions or topical hydrogen peroxide.Study limitations included no blinding, many dropouts, and no intention-to-treat analysis. Except for the severe application site reactions of imiquimod, none of the evaluated treatments described above were associated with serious adverse effects (low-quality evidence). Among the most common adverse events were pain during application, erythema, and itching. Included studies of the following comparisons did not report adverse effects: calcarea carbonica versus placebo, 10% povidone iodine plus 50% salicylic acid plaster versus salicylic acid plaster, and 10% benzoyl peroxide versus 0.05% tretinoin.We were unable to judge the risk of bias in most studies due to insufficient information, especially regarding concealment of allocation and possible selective reporting. We considered five studies to be at low risk of bias. AUTHORS' CONCLUSIONS: No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. We found moderate-quality evidence that topical 5% imiquimod was no more effective than vehicle in terms of clinical cure, but led to more application site reactions, and high-quality evidence that there was no difference between the treatments in terms of short-term improvement. However, high-quality evidence showed a similar number of general side effects in both groups. As the evidence found did not favour any one treatment, the natural resolution of molluscum contagiosum remains a strong method for dealing with the condition.
[Mh] Termos MeSH primário: Molusco Contagioso/terapia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/uso terapêutico
Aminoquinolinas/uso terapêutico
Anti-Infecciosos Locais/uso terapêutico
Peróxido de Benzoíla/uso terapêutico
Cimetidina/uso terapêutico
Seres Humanos
Hidróxidos/uso terapêutico
Molusco Contagioso/tratamento farmacológico
Myrtus
Azeite de Oliva/uso terapêutico
Fitoterapia/métodos
Óleos Vegetais/uso terapêutico
Compostos de Potássio/uso terapêutico
Povidona-Iodo/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Remissão Espontânea
Ácido Salicílico/uso terapêutico
Nitrito de Sódio/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Aminoquinolines); 0 (Anti-Infective Agents, Local); 0 (Hydroxides); 0 (Olive Oil); 0 (Plant Oils); 0 (Potassium Compounds); 80061L1WGD (Cimetidine); 85H0HZU99M (Povidone-Iodine); M0KG633D4F (Sodium Nitrite); O414PZ4LPZ (Salicylic Acid); P1QW714R7M (imiquimod); W9WZN9A0GM (Benzoyl Peroxide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD004767.pub4


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[PMID]:28272694
[Au] Autor:Shi YY; Liu HF; Min M; Wang W; Li J; He CY; Du QP
[Ad] Endereço:Department of Gastroenterology, Beijing Armed Police General Hospital, Beijing, China. duqiupengasd@163.com.
[Ti] Título:Correlation analysis of mast cells and EGFR with endoscopic application of tissue glue for treatment of peptic ulcer healing.
[So] Source:Eur Rev Med Pharmacol Sci;21(4):861-866, 2017 Feb.
[Is] ISSN:2284-0729
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To investigate the impact of tissue glue on mast cells (MC) and epidermal growth factor receptor (EGFR) in rat peptic ulcer. MATERIALS AND METHODS: SD rats were used to establish peptic ulcer model. Cimetidine gavage was adopted in the positive control, while cimetidine and endoscopic tissue glue therapy were applied in the experimental group. The ulcer inhibition rate and ulcer index were measured to evaluate healing quality. Real-time PCR was performed to test EGFR mRNA in the ulcer surrounded gastric mucosa. Immunohistochemistry was selected to determine MC quantity. HE staining and apoptosis detection were used to evaluate cell apoptosis. RESULTS: Tissue glue significantly reduced MC number in the peptic ulcer rat compared with control with dose dependence (p < 0.05). Tissue glue significantly decreased ulcer area, and elevated ulcer index and inhibition rate (p < 0.05). EGFR mRNA in the mucosa markedly declined after modeling. Tissue glue upregulated EGFR mRNA to a certain extent (p > 0.05). Tissue glue induced MC apoptosis with dose dependence. CONCLUSIONS: Endoscopic application of tissue glue accelerated ulcer mucosa healing via up-regulating EGFR mRNA, enhancing gastrointestinal mucous membrane regeneration and repair ability, and decreasing MC number.
[Mh] Termos MeSH primário: Mastócitos/citologia
Úlcera Péptica/terapia
Receptor do Fator de Crescimento Epidérmico/metabolismo
Adesivos Teciduais
[Mh] Termos MeSH secundário: Animais
Cimetidina/farmacologia
Mucosa Gástrica/metabolismo
Mucosa Gástrica/patologia
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tissue Adhesives); 80061L1WGD (Cimetidine); EC 2.7.10.1 (Egfr protein, rat); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE


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[PMID]:28160941
[Au] Autor:Céolin R; Rietveld IB
[Ad] Endereço:Letiam, EA7357, IUT Orsay, université Paris-Sud, rue Noetzlin, 91405 Orsay cedex, France.
[Ti] Título:The topological phase diagram of cimetidine: A case of overall monotropy.
[So] Source:Ann Pharm Fr;75(2):89-94, 2017 Mar.
[Is] ISSN:0003-4509
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Cimetidine is a histamine H -receptor antagonist used against peptic ulcers. It is known to exhibit crystalline polymorphism. Forms A and D melt within 0.35 degrees from each other and the enthalpies of fusion are similar as well. The present paper demonstrates how to construct a pressure-temperature phase diagram with only calorimetric and volumetric data available. The phase diagram provides the stability domains and the phase equilibria for the phases A, D, the liquid and the vapor. Cimetidine is overall monotropic with form D the only stable solid phase.
[Mh] Termos MeSH primário: Cimetidina/química
[Mh] Termos MeSH secundário: Calorimetria
Cristalização
Estabilidade de Medicamentos
Pressão
Temperatura Ambiente
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
80061L1WGD (Cimetidine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170206
[St] Status:MEDLINE


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[PMID]:28056407
[Au] Autor:Yu Y; Wang M; Zhang K; Yang D; Zhong Y; An J; Lei B; Zhang X
[Ad] Endereço:Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China. Electronic address: yuyingxin@staff.shu.edu.cn.
[Ti] Título:The transepithelial transport mechanism of polybrominated diphenyl ethers in human intestine determined using a Caco-2 cell monolayer.
[So] Source:Environ Res;154:93-100, 2017 04.
[Is] ISSN:1096-0953
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Oral ingestion plays an important role in human exposure to polybrominated diphenyl ethers (PBDEs). The uptake of PBDEs primarily occurs in the small intestine. The aim of the present study is to investigate the transepithelial transport characteristics and mechanisms of PBDEs in the small intestine using a Caco-2 cell monolayer model. The apparent permeability coefficients of PBDEs indicated that tri- to hepta-BDEs were poorly absorbed compounds. A linear increase in transepithelial transport was observed with various concentrations of PBDEs, which suggested that passive diffusion dominated their transport at the concentration range tested. In addition, the pseudo-first-order kinetics equation can be applied to the transepithelial transport of PBDEs. The rate-determining step in transepithelial transport of PBDEs was trans-cell transport including the trans-pore process. The significantly lower transepithelial transport rates at low temperature for bidirectional transepithelial transport suggested that an energy-dependent transport mechanism was involved. The efflux transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) and influx transporters (organic cation transporters) participated in the transepithelial transport of PBDEs. In addition, the transepithelial transport of PBDEs was pH sensitive; however, more information is required to understand the influence of pH.
[Mh] Termos MeSH primário: Poluentes Ambientais/farmacocinética
Éteres Difenil Halogenados/farmacocinética
[Mh] Termos MeSH secundário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Transporte Biológico
Células CACO-2/efeitos dos fármacos
Sobrevivência Celular
Cimetidina/farmacologia
Seres Humanos
Concentração de Íons de Hidrogênio
Intestinos/efeitos dos fármacos
Proteínas de Neoplasias/metabolismo
Temperatura Ambiente
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCG2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Environmental Pollutants); 0 (Halogenated Diphenyl Ethers); 0 (Neoplasm Proteins); 80061L1WGD (Cimetidine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE


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[PMID]:27798203
[Au] Autor:Nichol T; Smith TJ; Townsend R; Stockley I; Akid R
[Ad] Endereço:Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield, UK.
[Ti] Título:Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement.
[So] Source:J Antimicrob Chemother;72(2):410-416, 2017 Feb.
[Is] ISSN:1460-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To assess the Gram-positive-specific antibiotic linezolid and the broad-spectrum antibiotic tigecycline for use in local antibiotic delivery via antibiotic-loaded bone cement. METHODS: Linezolid and tigecycline were added to Biomet bone cement at varying concentrations. Antibiotic elution over 1 week was quantified by HPLC-MS. The effect of wear on elution over 51 h was determined using a modified TE-66 wear tester. Eluted antibiotics were used to determine the MICs for a panel of clinically relevant bacteria. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. Cytotoxicity of eluted antibiotics against MG-63 cells was evaluated using an MTT assay. RESULTS: Linezolid and tigecycline eluted from bone cement to clinically relevant levels within 1 h and retained activity over 1 week. Mechanical wear significantly reduced elution of tigecycline, but had little effect on elution of linezolid. Linezolid showed low cytotoxicity towards MG-63 cells with ≤300 mg/mL resulting in >50% cell activity. Cytotoxicity of tigecycline was higher, with an IC of 5-10 mg/L. CONCLUSIONS: Linezolid and tigecycline retain activity after elution from bone cement. The concentration of tigecycline may need to be carefully controlled due to cytotoxicity. The effect of wear on bone cement may need to be considered if tigecycline is to be used for local delivery. Up to 10% linezolid can be added without affecting the impact strength of the bone cement. These results are promising indications for future investigation of these antibiotics for use in local antibiotic delivery strategies.
[Mh] Termos MeSH primário: Antibacterianos/farmacocinética
Cimetidina/química
Linezolida/farmacocinética
Minociclina/análogos & derivados
[Mh] Termos MeSH secundário: Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Cromatografia Líquida de Alta Pressão
Portadores de Fármacos
Seres Humanos
Concentração Inibidora 50
Espectrometria de Massas
Testes de Sensibilidade Microbiana
Minociclina/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Drug Carriers); 70JE2N95KR (tigecycline); 80061L1WGD (Cimetidine); FYY3R43WGO (Minocycline); ISQ9I6J12J (Linezolid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE
[do] DOI:10.1093/jac/dkw410


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[PMID]:27739140
[Au] Autor:Goineau S; Castagné V
[Ad] Endereço:Porsolt S.A.S., Z.A. de Glatigné, 53940, Le Genest-Saint-Isle, France.
[Ti] Título:Complementarity of in vitro and in vivo models for the evaluation of gastro-protective effects of pharmacological substances.
[So] Source:Fundam Clin Pharmacol;31(2):155-164, 2017 Apr.
[Is] ISSN:1472-8206
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gastric mucosa is frequently exposed to various gastric irritants, and there is a continuing requirement to develop new gastro-protective agents. This study compares the effects of three such agents, sucralfate, rebamipide, and cimetidine in both in vivo and in vitro indomethacin-induced gastric damage models. For the in vivo approach, rats were orally administered sucralfate, rebamipide, and cimetidine at 300 mg/kg before an acute dose of indomethacin (30 mg/kg). Gastric lesions were then macroscopically examined. For the in vitro approach, gastric mucosal cells were incubated with sucralfate (3 and 5 mg/mL), rebamipide (0.3 and 1 mm), and cimetidine (10 and 50 µg/mL) before exposure to indomethacin (3.8 mm). The release of lactate dehydrogenase (LDH) and mitochondrial function were then measured. Sucralfate, rebamipide, and cimetidine displayed gastro-protective effects in vivo (decreased number of gastric ulcers: -50% P < 0.05, -22% NS, and -69% P < 0.05, respectively, and reduced length of gastric lesions: -62% P < 0.05, -29% NS, and -70% P < 0.001, respectively). Cell damage induced by indomethacin in vitro was inhibited by sucralfate (LDH release) and by rebamipide and cimetidine (mitochondrial function and LDH release). In contrast, sucralfate accentuated the indomethacin-induced decrease in mitochondrial function. Although cultured gastric cells offer a promising tool for evaluating the cytotoxic or protective effects of test compounds, data from in vivo models are still needed to confirm in vitro data. Using both approaches provides more comprehensive insight into the effects of test compounds on the gastric mucosa.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Cimetidina/farmacologia
Mucosa Gástrica/efeitos dos fármacos
Quinolonas/farmacologia
Úlcera Gástrica/prevenção & controle
Sucralfato/farmacologia
[Mh] Termos MeSH secundário: Alanina/administração & dosagem
Alanina/farmacologia
Animais
Antiulcerosos/administração & dosagem
Antiulcerosos/farmacologia
Cimetidina/administração & dosagem
Relação Dose-Resposta a Droga
Mucosa Gástrica/patologia
Indometacina/toxicidade
L-Lactato Desidrogenase/metabolismo
Masculino
Mitocôndrias/patologia
Quinolonas/administração & dosagem
Ratos
Ratos Sprague-Dawley
Úlcera Gástrica/induzido quimicamente
Sucralfato/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Ulcer Agents); 0 (Quinolones); 54182-58-0 (Sucralfate); 80061L1WGD (Cimetidine); EC 1.1.1.27 (L-Lactate Dehydrogenase); LR583V32ZR (rebamipide); OF5P57N2ZX (Alanine); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170620
[Lr] Data última revisão:
170620
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161015
[St] Status:MEDLINE
[do] DOI:10.1111/fcp.12248


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[PMID]:27292271
[Au] Autor:Knych HK; Stanley SD; Arthur RM; McKemie DS
[Ad] Endereço:K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
[Ti] Título:Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.
[So] Source:J Vet Pharmacol Ther;40(1):92-96, 2017 Jan.
[Is] ISSN:1365-2885
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection.
[Mh] Termos MeSH primário: Antiulcerosos/farmacocinética
Cimetidina/farmacocinética
Cavalos/metabolismo
Omeprazol/farmacocinética
Ranitidina/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Antiulcerosos/administração & dosagem
Antiulcerosos/sangue
Cimetidina/administração & dosagem
Cimetidina/sangue
Esquema de Medicação/veterinária
Feminino
Meia-Vida
Masculino
Omeprazol/administração & dosagem
Omeprazol/sangue
Condicionamento Físico Animal
Ranitidina/administração & dosagem
Ranitidina/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Ulcer Agents); 80061L1WGD (Cimetidine); 884KT10YB7 (Ranitidine); KG60484QX9 (Omeprazole)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160614
[St] Status:MEDLINE
[do] DOI:10.1111/jvp.12328


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[PMID]:27209586
[Au] Autor:Mariotti F; Ciurlia G; Spaccapelo L; Muraro A; Acerbi D
[Ad] Endereço:Global Clinical Development, Chiesi Farmaceutici SpA, Largo Belloli 11/A, 43122, Parma, Italy. F.Mariotti@chiesi.com.
[Ti] Título:A Two-Period Open-Label, Single-Dose Crossover Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Between Cimetidine and Inhaled Extrafine CHF 5993.
[So] Source:Eur J Drug Metab Pharmacokinet;42(2):269-279, 2017 Apr.
[Is] ISSN:2107-0180
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVES: CHF 5993 is an extrafine 'triple therapy' combination of the long-acting muscarinic antagonist glycopyrronium bromide (GB), the long-acting ß -agonist formoterol fumarate (FF), and the inhaled corticosteroid beclometasone dipropionate (BDP). It is in development for chronic obstructive pulmonary disease and asthma delivered via pressurised metered-dose inhaler. METHODS: This two-period, open-label, crossover study examined the drug-drug interaction of CHF 5993 and cimetidine. In one period, subjects received cimetidine 800 mg twice daily for 6 days; on the fourth day they also received CHF 5993 (BDP/FF/GB 400/24/100 µg). In the other, they received CHF 5993 alone. Primary objective was to compare the area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC ) of GB, with and without cimetidine. Secondary endpoints included GB AUC , maximum concentration (C ), time to C (t ), elimination half-life (t ) and urinary excretion. Pharmacokinetic parameters of BDP, beclometasone-17-monopropionate (B17MP; active metabolite of BDP) and formoterol were also evaluated. RESULTS: Twenty-six subjects were randomised; 25 completed. Co-administration of CHF 5993 and cimetidine resulted in small, statistically significant increases in GB AUC , AUC and C vs CHF 5993 (ratios 1.16, 1.21 and 1.26, respectively); t , t and urinary excretion were unaffected. There were small, statistically significant increases in formoterol AUC , AUC and t following co-administration of cimetidine and CHF 5993; urinary excretion was unaffected. There were no significant differences for either BDP or B17MP. There were few adverse events (AEs), and no serious AEs. CONCLUSIONS: Overall, this study indicates that there is no clinically relevant drug-drug interaction between CHF 5993 and cimetidine.
[Mh] Termos MeSH primário: Beclometasona/farmacocinética
Cimetidina/farmacologia
Fumarato de Formoterol/farmacocinética
Glicopirrolato/farmacocinética
[Mh] Termos MeSH secundário: Administração por Inalação
Adulto
Antiasmáticos/administração & dosagem
Antiasmáticos/farmacocinética
Área Sob a Curva
Broncodilatadores/administração & dosagem
Broncodilatadores/farmacocinética
Cimetidina/administração & dosagem
Estudos Cross-Over
Combinação de Medicamentos
Interações Medicamentosas
Feminino
Fumarato de Formoterol/administração & dosagem
Glicopirrolato/administração & dosagem
Meia-Vida
Seres Humanos
Masculino
Inaladores Dosimetrados
Meia-Idade
Antagonistas Muscarínicos/administração & dosagem
Antagonistas Muscarínicos/farmacocinética
Tamanho da Partícula
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Asthmatic Agents); 0 (Bronchodilator Agents); 0 (Drug Combinations); 0 (Muscarinic Antagonists); 80061L1WGD (Cimetidine); KGZ1SLC28Z (Beclomethasone); V92SO9WP2I (Glycopyrrolate); W34SHF8J2K (Formoterol Fumarate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160523
[St] Status:MEDLINE
[do] DOI:10.1007/s13318-016-0345-2


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[PMID]:27781273
[Au] Autor:Hansmann S; Darwich A; Margolskee A; Aarons L; Dressman J
[Ad] Endereço:Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
[Ti] Título:Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models.
[So] Source:J Pharm Pharmacol;68(12):1501-1515, 2016 Dec.
[Is] ISSN:2042-7158
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The aim of this study was (1) to determine how closely physiologically based pharmacokinetic (PBPK) models can predict oral bioavailability using a priori knowledge of drug-specific properties and (2) to examine the influence of the biopharmaceutics classification system class on the simulation success. METHODS: Simcyp Simulator, GastroPlus and GI-Sim were used. Compounds with published Biowaiver monographs (bisoprolol (BCS I), nifedipine (BCS II), cimetidine (BCS III), furosemide (BCS IV)) were selected to ensure availability of accurate and reproducible data for all required parameters. Simulation success was evaluated with the average fold error (AFE) and absolute average fold error (AAFE). Parameter sensitivity analysis (PSA) to selected parameters was performed. KEY FINDINGS: Plasma concentration-time profiles after intravenous administration were forecast within an AAFE < 3. The addition of absorption processes resulted in more variability in the prediction of the plasma profiles, irrespective of biopharmaceutics classification system (BCS) class. The reliability of literature permeability data was identified as a key issue in the accuracy of predicting oral drug absorption. CONCLUSION: For the four drugs studied, it appears that the forecasting accuracy of the PBPK models is related to the BCS class (BCS I > BCS II, BCS III > BCS IV). These results will need to be verified with additional drugs.
[Mh] Termos MeSH primário: Biofarmácia/métodos
Bisoprolol/farmacocinética
Cimetidina/farmacocinética
Furosemida/farmacocinética
Absorção Gastrointestinal
Modelos Biológicos
Nifedipino/farmacocinética
[Mh] Termos MeSH secundário: Administração Intravenosa
Administração Oral
Animais
Disponibilidade Biológica
Biotransformação
Bisoprolol/administração & dosagem
Bisoprolol/química
Bisoprolol/classificação
Cimetidina/administração & dosagem
Cimetidina/química
Cimetidina/classificação
Simulação por Computador
Composição de Medicamentos
Previsões
Furosemida/administração & dosagem
Furosemida/química
Furosemida/classificação
Seres Humanos
Nifedipino/administração & dosagem
Nifedipino/química
Nifedipino/classificação
Permeabilidade
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
7LXU5N7ZO5 (Furosemide); 80061L1WGD (Cimetidine); I9ZF7L6G2L (Nifedipine); Y41JS2NL6U (Bisoprolol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE
[do] DOI:10.1111/jphp.12618



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