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[PMID]:28442642
[Au] Autor:Tugcu-Demiröz F
[Ad] Endereço:Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University.
[Ti] Título:Vaginal Delivery of Benzydamine Hydrochloride through Liposomes Dispersed in Mucoadhesive Gels.
[So] Source:Chem Pharm Bull (Tokyo);65(7):660-667, 2017 Jul 01.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (-1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm , while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm . N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.
[Mh] Termos MeSH primário: Benzidamina/administração & dosagem
Derivados da Hipromelose
[Mh] Termos MeSH secundário: Acrilatos/química
Adesividade
Administração Intravaginal
Benzidamina/química
Benzidamina/farmacocinética
Química Farmacêutica
Difusão
Liberação Controlada de Fármacos
Estabilidade de Medicamentos
Feminino
Géis/química
Seres Humanos
Derivados da Hipromelose/química
Lipossomos/química
Vagina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acrylates); 0 (Gels); 0 (Liposomes); 0 (carbopol 974P NF); 3NXW29V3WO (Hypromellose Derivatives); 4O21U048EF (Benzydamine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00133


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[PMID]:28258069
[Au] Autor:Uehara S; Shimizu M; Uno Y; Inoue T; Sasaki E; Yamazaki H
[Ad] Endereço:Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan (S.U., M.S., H.Y.); Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama, Japan (Y.U.); Department of Applied Developmental Biology (T.I.) and Ce
[Ti] Título:Marmoset Flavin-Containing Monooxygenase 3 in the Liver Is a Major Benzydamine and Sulindac Sulfide Oxygenase.
[So] Source:Drug Metab Dispos;45(5):497-500, 2017 May.
[Is] ISSN:1521-009X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Common marmosets ( ) are potentially primate models for preclinical drug metabolism studies because there are similarities in the molecular characteristics of cytochrome P450 enzymes between this species and humans. However, characterization of non-cytochrome P450 enzymes has not been clarified in marmosets. Here, we report characterization of flavin-containing monooxygenases FMO1-FMO5 identified in marmoset tissues. Marmoset FMO forms shared high amino acid sequence identities (93%-95%) and phylogenetic closeness with human homologous FMO forms. FMO1 and FMO3 mRNA were abundantly expressed in the liver and kidneys among five marmoset tissues examined, where FMO3 protein was detected by immunoblotting. FMO inhibition assays using preheated tissue microsomes indicated that benzydamine -oxygenation and sulindac sulfide -oxygenation in the marmoset liver was mainly catalyzed by FMO3, the major hepatic FMO. Marmoset FMO3 protein heterologously expressed in effectively catalyzed benzydamine -oxygenation and sulindac sulfide -oxygenation comparable to marmoset liver microsomes. These results indicate that the FMO3 enzyme expressed in marmoset livers mainly metabolizes benzydamine and sulindac sulfide (typical human FMO substrates), suggesting its importance for FMO-dependent drug metabolism in marmosets.
[Mh] Termos MeSH primário: Benzidamina/farmacocinética
Callithrix
Fígado/enzimologia
Oxigenases/metabolismo
Sulindaco/análogos & derivados
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Callithrix/genética
Callithrix/metabolismo
Avaliação Pré-Clínica de Medicamentos/métodos
Escherichia coli/genética
Feminino
Temperatura Alta
Seres Humanos
Masculino
Microssomos Hepáticos/enzimologia
Especificidade de Órgãos
Oxigenases/genética
Homologia de Sequência de Aminoácidos
Especificidade da Espécie
Sulindaco/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
184SNS8VUH (Sulindac); 4O21U048EF (Benzydamine); 6UVA8S2DEY (sulindac sulfide); EC 1.13.- (Oxygenases); EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming))
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE
[do] DOI:10.1124/dmd.117.075184


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[PMID]:28137602
[Au] Autor:Catucci G; Polignano I; Cusumano D; Medana C; Gilardi G; Sadeghi SJ
[Ad] Endereço:Department of Life Sciences and Systems Biology, University of Torino, 10123 Turin, Italy.
[Ti] Título:Identification of human flavin-containing monooxygenase 3 substrates by a colorimetric screening assay.
[So] Source:Anal Biochem;522:46-52, 2017 Apr 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human hepatic flavin-containing monooxygenase 3 is a phase I drug-metabolizing enzyme that is responsible for the oxidation of a variety of drugs and xenobiotics. This work reports on a high throughput rapid colorimetric assay for the screening of substrates or inhibitors of this enzyme. The method is based on the competition of two substrates for access to the active site of hFMO3 whereby the enzymatic product of the first drug converts nitro-5-thiobenzoate (TNB, yellow) to 5,5'-dithiobis (2-nitrobenzoate) (DTNB, colourless). Upon addition of a competing substrate, the amount of detected DNTB is decreased. The assay is validated testing three known substrates of hFMO3, namely benzydamine, tozasertib and tamoxifen. The latter drugs resulted in 41%-55% inhibition. In addition, two other drugs also classified as doping drugs, selegiline and clomiphene, were selected based on their chemical structure similarity to known substrates of hFMO3. These drugs showed 21% and 60% inhibition in the colorimetric assay and therefore were proven to be hFMO3 substrates. LC-MS was used to confirm their N-oxide products. Further characterisation of these newly identified hFMO3 substrates was performed determining their K and k values that resulted to be 314 µM and 1.4 min for selegiline and, 18 µM and 0.1 min for clomiphene. This method paves the way for a rapid automated high throughput screening of nitrogen-containing compounds as substrates/inhibitors of hFMO3.
[Mh] Termos MeSH primário: Benzoatos/química
Benzidamina/química
Ácido Ditionitrobenzoico/química
Oxigenases/química
Piperazinas/química
Polietilenoglicóis/química
Tamoxifeno/química
[Mh] Termos MeSH secundário: Colorimetria/métodos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoates); 0 (Piperazines); 0 (thiobenzoate chromophore); 094ZI81Y45 (Tamoxifen); 30IQX730WE (Polyethylene Glycols); 4O21U048EF (Benzydamine); 639089-54-6 (VX680); 9BZQ3U62JX (Dithionitrobenzoic Acid); EC 1.13.- (Oxygenases); EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming))
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE


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[PMID]:27987094
[Au] Autor:Rastogi M; Khurana R; Revannasiddaiah S; Jaiswal I; Nanda SS; Gupta P; Chufal KS; Bhatt ML
[Ad] Endereço:Department of Radiation Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Gomti Nagar, Lucknow, 226010, India. drmadhup1@rediffmail.com.
[Ti] Título:Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy.
[So] Source:Support Care Cancer;25(5):1439-1443, 2017 May.
[Is] ISSN:1433-7339
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Benzydamine is recommended for prophylaxis of oral mucositis (OM) in head and neck cancer (HNC) patients for radiation doses (<50 Gy). This study evaluates role of benzydamine for higher radiation doses (>50 Gy) with or without chemotherapy. METHODS: One hundred twenty patients of HNC with planned radiation doses of ≥60 Gy were randomized to group A (control radiotherapy alone), group B (study radiotherapy alone), group C (control chemoradiotherapy), or to group D (study chemoradiotherapy). Groups A and C were advised saline mouth rinses, and in groups B and D, additional benzydamine rinses (0.15%) were advised. Mucositis grading was done with both WHO (WHO-M) and CTCAE (CTC-M) version 4.0 (common terminology criteria for adverse events) weekly. RESULTS: Patient characteristics are presented in the table. Patients in group B had lesser grade 3 WHO-M and CTC-M as compared to group A, 62.1 vs. 36.4% (p = 0.038) and 51.7 vs. 27.3% (p = 0.043), respectively. The rates of Ryle's tube feeding (RTF), intravenous fluid supplementation (IVF), and hospitalization were also lesser in group B as compared to A, 34.5 vs. 21.2% (p = 0.18), 27.6 vs. 9.1% (p = 0.06), and 6.9 vs. 0% (p = 0.21), respectively. WHO-M and CTC-M in groups C and D were not statistically different, 64.3 vs. 43.3% (p = 0.091) and 53.6% vs. 43.3% (p = 0.30), respectively. The rates of RTF, IVF, and hospitalization were all lesser but p > 0.05. CONCLUSION: Benzydamine significantly reduces OM even at doses >50 Gy in HNC patients. Its role in patients receiving concurrent chemotherapy further needs to be evaluated.
[Mh] Termos MeSH primário: Benzidamina/uso terapêutico
Carcinoma de Células Escamosas/radioterapia
Neoplasias de Cabeça e Pescoço/radioterapia
Lesões por Radiação/prevenção & controle
Estomatite/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Carcinoma de Células Escamosas/tratamento farmacológico
Quimiorradioterapia/efeitos adversos
Relação Dose-Resposta à Radiação
Feminino
Neoplasias de Cabeça e Pescoço/tratamento farmacológico
Seres Humanos
Masculino
Meia-Idade
Antissépticos Bucais/uso terapêutico
Estudos Prospectivos
Lesões por Radiação/etiologia
Estomatite/etiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Mouthwashes); 4O21U048EF (Benzydamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161218
[St] Status:MEDLINE
[do] DOI:10.1007/s00520-016-3548-9


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[PMID]:28195065
[Au] Autor:Mathivanan S; de la Torre-Martinez R; Wolf C; Mangano G; Polenzani L; Milanese C; Ferrer-Montiel A
[Ad] Endereço:Institute of Molecular and Cell Biology, Miguel Hernandez University, Alicante, Spain. aferrer@umh.es.
[Ti] Título:Effect of econazole and benzydamine on sensory neurons in culture.
[So] Source:J Physiol Pharmacol;67(6):851-858, 2016 Dec.
[Is] ISSN:1899-1505
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:Econazole is an anti-mycotic agent widely used for the treatment of cutaneous fungal infections, and for the therapy of vaginal candidiasis. Topical application of this azole is generally safe, although some patients have complained of mild burning sensation/cutaneous irritation and itching, especially when administered intravaginally. The underlying mechanisms responsible of these adverse effects are poorly understood, though they suggest excitation of cutaneous nociceptor terminals. We report that exposure of primary cultures of rat nociceptors to econazole augments neuronal excitability. This effect appears mediated by increments in the intracellular Ca by stimulating Ca entry and release from the endoplasmic reticulum. Ca entry was not due to activation of thermo transient receptor potential (TRP) channels, suggesting a different ion channel targeted by the azole. Noteworthy, econazole-evoked responses were potentiated by a pro-inflammatory agent, which resulted in an increase in neuronal excitability. Econazole-elicited action potential firing was significantly abolished by the inflammatory cytokine inhibiting drug benzydamine via blockade of voltage-gated Na (Nav) channels. Collectively, our results indicate that the burning sensation of econazole is due at least in part to modulation of nociceptor excitability, and such sensation is increased in the presence of pro-inflammatory stimuli and blocked by benzydamine. These findings imply that a combination of the azole with benzydamine has the potential to reduce significantly the unpleasant symptoms related to infection and to the adverse effects of topical econazole formulations.
[Mh] Termos MeSH primário: Benzidamina/farmacologia
Econazol/farmacologia
Células Receptoras Sensoriais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antifúngicos/farmacologia
Cálcio/metabolismo
Células Cultivadas
Citocinas/metabolismo
Retículo Endoplasmático/efeitos dos fármacos
Retículo Endoplasmático/metabolismo
Inflamação/tratamento farmacológico
Inflamação/metabolismo
Nociceptores/efeitos dos fármacos
Nociceptores/metabolismo
Ratos
Ratos Wistar
Células Receptoras Sensoriais/metabolismo
Canais de Receptores Transientes de Potencial/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Cytokines); 0 (Transient Receptor Potential Channels); 4O21U048EF (Benzydamine); 6Z1Y2V4A7M (Econazole); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170215
[St] Status:MEDLINE


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[PMID]:27108819
[Au] Autor:Mekhemar NA; El-Agwany AS; Radi WK; El-Hady SM
[Ad] Endereço:Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. Electronic address: Nashwaabdallah287@gmail.com.
[Ti] Título:Comparative study between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on endotracheal tube cuff as regards postoperative sore throat.
[So] Source:Braz J Anesthesiol;66(3):242-8, 2016 May-Jun.
[Is] ISSN:0104-0014
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Postoperative sore throat is a common complication after endotracheal intubation. After tracheal intubation, the incidence of sore throat varies from 14.4% to 50%. The aim of the study was to compare between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on the endotracheal tube cuff as regards postoperative sore throat. The present study was carried out on 124 patients admitted to Alexandria university hospitals for lumbar fixation surgery requiring general anesthesia. Patients were randomly allocated into 4 groups. Benzydamine hydrochloride gel, 5% lidocaine hydrochloride gel, 10% lidocaine hydrochloride spray, or normal saline were applied on endotracheal tube cuffs before endotracheal intubation. The patients were examined for sore throat (none, mild, moderate, or severe) at 0, 1, 6, 12, and 24h after extubation. The results were collected, analyzed and presented in table and figure. The highest incidence of postoperative sore throat occurred at 6h after extubation in all groups. There was a significantly lower incidence of postoperative sore throat in the benzydamine group than 5% lidocaine gel, 10% lidocaine spray, and normal saline groups. The benzydamine group had significantly decreased severity of postoperative sore throat compared with the 10% lidocaine, 5% lidocaine, and normal saline groups at observation time point. Compared with the 5% lidocaine the 10% lidocaine group had significantly increased incidence and severity of postoperative sore throat after extubation. Compared with normal saline the 10% lidocaine group had increased incidence of postoperative sore throat. There were no significant differences among groups in local or systemic side effects. So in conclusion, benzydamine hydrochloride gel on the endotracheal tube cuff is a simple and effective method to reduce the incidence and severity of postoperative sore throat. Application of 10% lidocaine spray should be avoided because of worsening of postoperative sore throat where incidence increased but not the severity in relation to 5% lidocaine gel. Applying 5% lidocaine on the endotracheal tube cuff does not prevent postoperative sore throat but its application is better than lidocaine 10% spray or saline.
[Mh] Termos MeSH primário: Benzidamina/uso terapêutico
Intubação Intratraqueal/efeitos adversos
Lidocaína/uso terapêutico
Faringite/prevenção & controle
Complicações Pós-Operatórias/prevenção & controle
[Mh] Termos MeSH secundário: Administração por Inalação
Adulto
Anestésicos Locais/administração & dosagem
Anestésicos Locais/uso terapêutico
Anti-Inflamatórios/administração & dosagem
Anti-Inflamatórios/uso terapêutico
Benzidamina/administração & dosagem
Relação Dose-Resposta a Droga
Feminino
Géis/uso terapêutico
Seres Humanos
Lidocaína/administração & dosagem
Masculino
Meia-Idade
Nebulizadores e Vaporizadores
Índice de Gravidade de Doença
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Local); 0 (Anti-Inflammatory Agents); 0 (Gels); 4O21U048EF (Benzydamine); 98PI200987 (Lidocaine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170503
[Lr] Data última revisão:
170503
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160426
[St] Status:MEDLINE


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[PMID]:26149601
[Au] Autor:Chang JE; Min SW; Kim CS; Han SH; Kwon YS; Hwang JY
[Ad] Endereço:Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Boramae-ro, Dongjak-gu, Seoul, 156-707, Republic of Korea.
[Ti] Título:Effect of prophylactic benzydamine hydrochloride on postoperative sore throat and hoarseness after tracheal intubation using a double-lumen endobronchial tube: a randomized controlled trial.
[So] Source:Can J Anaesth;62(10):1097-103, 2015 Oct.
[Is] ISSN:1496-8975
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: We evaluated the prophylactic effect of benzydamine hydrochloride (BH) spray on postoperative sore throat and hoarseness secondary to intubation with a double-lumen endobronchial tube (DLT). METHODS: Ninety-two adult patients undergoing thoracic surgery using DLT intubation were studied. The DLT cuff and oropharyngeal cavity were sprayed with normal saline (Group S; n = 46) or BH (Group BH; n = 46) prior to intubation. Postoperative sore throat and hoarseness were evaluated at one, six, and 24 hr after surgery. Sore throat was evaluated using a 0-100 mm visual analogue scale (VAS). Hoarseness was defined as a change in voice quality. RESULTS: Compared with Group S, postoperative sore throat occurred less frequently in Group BH at one hour (mean difference, 28.3%; 95% confidence interval [CI], 8.7 to 45.1; P = 0.01), at six hours (mean difference, 32.6%; 95% CI, 12.6 to 49.2; P < 0.01), and at 24 hr (mean difference, 28.3%; 95% CI, 9.3 to 44.7; P = 0.01) after surgery. Group BH had lower VAS scores for postoperative sore throat at one hour (mean difference, 12.8; 95% CI, 4.9 to 20.7), at six hours (mean difference, 11.9; 95% CI, 4.8 to 19.1; P < 0.01), and at 24 hr (mean difference, 5.3; 95% CI, 0.9 to 9.7; P = 0.01) after surgery. Hoarseness also occurred less frequently in Group BH at one hour (mean difference, 23.9%; 95% CI, 6.8 to 39.6; P = 0.01), at six hours (mean difference, 23.9%; 95% CI, 7.4 to 39.3; P = 0.01), and at 24 hr (mean difference, 21.7%; 95% CI, 5.5 to 37.0; P = 0.02) after surgery (P < 0.01). CONCLUSIONS: Prophylactic application of BH to the DLT cuff and oropharyngeal cavity reduces the incidence and severity of postoperative sore throat and the incidence of hoarseness associated with DLT intubation. The trial was registered at the Clinical Research Information Service (KCT0001068).
[Mh] Termos MeSH primário: Benzidamina/administração & dosagem
Rouquidão/prevenção & controle
Intubação Intratraqueal/efeitos adversos
Faringite/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Rouquidão/epidemiologia
Rouquidão/etiologia
Seres Humanos
Incidência
Intubação Intratraqueal/métodos
Masculino
Meia-Idade
Medição da Dor
Faringite/epidemiologia
Faringite/etiologia
Complicações Pós-Operatórias/epidemiologia
Complicações Pós-Operatórias/etiologia
Complicações Pós-Operatórias/prevenção & controle
Período Pós-Operatório
Índice de Gravidade de Doença
Fatores de Tempo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
4O21U048EF (Benzydamine)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150905
[Lr] Data última revisão:
150905
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150708
[St] Status:MEDLINE
[do] DOI:10.1007/s12630-015-0432-x


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[PMID]:26006195
[Au] Autor:Ibis M; Arhan M; Ibis T; Önal IK; Erdal H; Utku ÖG
[Ad] Endereço:Department of Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey. ibismehmet@yahoo.com.
[Ti] Título:Lidocaine versus lidocaine plus benzydamine as a topical anesthesia regimen for unsedated upper gastrointestinal endoscopy: A comparison study.
[So] Source:Turk J Gastroenterol;26(3):224-7, 2015 May.
[Is] ISSN:2148-5607
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The aim was to assess the efficacy of adding benzydamine (B) spray to standard treatment with a lidocaine (L) spray before upper gastrointestinal endoscopy (UGE) as a topical anaesthetic regimen. MATERIALS AND METHODS: A total of 118 adult patients undergoing outpatient UGE were randomly assigned to receive L (n=44), LB (n=38) or B (n=36) before the procedure. The primary outcome was the patient tolerance score, which represents a summative evaluation of the taste of the anesthetic agent, the intensity of pharyngeal numbness, the amount of coughing or gagging and the degree of discomfort during oesophageal intubation. RESULTS: The median (min-max) patient tolerance scores were comparable between groups LB (10.5; range 5-12) and L (10; range 4-13) (p=0.235) and significantly lower in group B (7.5; range 3-12) (p<0.01). LB improved several secondary outcomes. Oesophageal intubation was less difficult (5 [range 2-10] vs 3 [range 0-8], p<0.001), and a lower proportion of patients developed postprocedural sore throat (4 [10.5%] vs 15 [34.1%], p=0.011) in LB compared to L. CONCLUSION: LB is not superior to L in terms of overall patient tolerance, but LB may be preferred over L in cases with difficult oesophageal intubation or a previous history of postprocedural sore throat.
[Mh] Termos MeSH primário: Anestesia Local/métodos
Anestésicos Combinados/administração & dosagem
Anestésicos Locais/administração & dosagem
Anti-Inflamatórios/administração & dosagem
Benzidamina/administração & dosagem
Endoscopia Gastrointestinal/métodos
Lidocaína/administração & dosagem
[Mh] Termos MeSH secundário: Administração Tópica
Adulto
Anestesia Local/psicologia
Esôfago
Feminino
Seres Humanos
Intubação Gastrointestinal/efeitos adversos
Masculino
Meia-Idade
Satisfação do Paciente
Faringe
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anesthetics, Combined); 0 (Anesthetics, Local); 0 (Anti-Inflammatory Agents); 4O21U048EF (Benzydamine); 98PI200987 (Lidocaine)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150526
[Lr] Data última revisão:
150526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150527
[St] Status:MEDLINE
[do] DOI:10.5152/tjg.2015.0090


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[PMID]:25760532
[Au] Autor:Shimizu M; Shiraishi A; Sato A; Nagashima S; Yamazaki H
[Ad] Endereço:Laboratory of DMPK, Showa Pharmaceutical University, 3-3165 Higashi-tamagawa Gakuen, Machida, Tokyo 194-8543, Japan.
[Ti] Título:Potential for drug interactions mediated by polymorphic flavin-containing monooxygenase 3 in human livers.
[So] Source:Drug Metab Pharmacokinet;30(1):70-4, 2015 Feb.
[Is] ISSN:1880-0920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human flavin-containing monooxygenase 3 (FMO3) in the liver catalyzes a variety of oxygenations of nitrogen- and sulfur-containing medicines and xenobiotic substances. Because of growing interest in drug interactions mediated by polymorphic FMO3, benzydamine N-oxygenation by human FMO3 was investigated as a model reaction. Among the 41 compounds tested, trimethylamine, methimazole, itopride, and tozasertib (50 µM) suppressed benzydamine N-oxygenation at a substrate concentration of 50 µM by approximately 50% after co-incubation. Suppression of N-oxygenation of benzydamine, trimethylamine, itopride, and tozasertib and S-oxygenation of methimazole and sulindac sulfide after co-incubation with the other five of these six substrates was compared using FMO3 proteins recombinantly expressed in bacterial membranes. Apparent competitive inhibition by methimazole (0-50 µM) of sulindac sulfide S-oxygenation was observed with FMO3 proteins. Sulindac sulfide S-oxygenation activity of Arg205Cys variant FMO3 protein was likely to be suppressed more by methimazole than wild-type or Val257Met variant FMO3 protein was. These results suggest that genetic polymorphism in the human FMO3 gene may lead to changes of drug interactions for N- or S-oxygenations of xenobiotics and endogenous substances and that a probe battery system of benzydamine N-oxygenation and sulindac sulfide S-oxygenation activities is recommended to clarify the drug interactions mediated by FMO3.
[Mh] Termos MeSH primário: Benzidamina/metabolismo
Microssomos Hepáticos/metabolismo
Oxigenases/genética
Oxigenases/metabolismo
Preparações Farmacêuticas/metabolismo
Polimorfismo Genético
[Mh] Termos MeSH secundário: Benzidamina/química
Catálise
Interações Medicamentosas
Seres Humanos
Técnicas In Vitro
Microssomos Hepáticos/enzimologia
Preparações Farmacêuticas/química
Proteínas Recombinantes
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Pharmaceutical Preparations); 0 (Recombinant Proteins); 4O21U048EF (Benzydamine); EC 1.13.- (Oxygenases); EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming))
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150312
[Lr] Data última revisão:
150312
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150312
[St] Status:MEDLINE


  10 / 311 MEDLINE  
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[PMID]:25760531
[Au] Autor:Taniguchi-Takizawa T; Shimizu M; Kume T; Yamazaki H
[Ad] Endereço:DMPK Research Laboratories, Research Division, Mitsubishi Tanabe Pharma Corporation, Toda, Saitama, Japan.
[Ti] Título:Benzydamine N-oxygenation as an index for flavin-containing monooxygenase activity and benzydamine N-demethylation by cytochrome P450 enzymes in liver microsomes from rats, dogs, monkeys, and humans.
[So] Source:Drug Metab Pharmacokinet;30(1):64-9, 2015 Feb.
[Is] ISSN:1880-0920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Benzydamine is an anti-inflammatory drug that undergoes flavin-containing monooxygenase (FMO)-dependent metabolism to benzydamine N-oxide; however, benzydamine N-demethylation is also catalyzed by liver microsomes. In this study, benzydamine N-oxygenation and N-demethylation mediated by liver microsomes from rats, dogs, monkeys, and humans were characterized comprehensively. Values of the maximum velocity/Michaelis constant ratio for benzydamine N-oxygenation by liver microsomes from dogs and rats were higher than those from monkeys and humans, despite roughly similar rates of N-demethylation in the four species. Benzydamine N-oxygenation by liver microsomes was extensively suppressed by preheating liver microsomes at 45 °C for 5 min or at 37 °C for 5-10 min without NADPH, and benzydamine N-demethylation was strongly inhibited by 1-aminbobenztriazole. Liver microsomal benzydamine N-oxygenation was inhibited by dimethyl sulfoxide and methimazole, whereas N-demethylation was inhibited by quinidine. High benzydamine N-oxygenation activities of recombinant human FMO1 and FMO3 and human kidney microsomes were observed at pH 8.4, whereas N-demethylation by cytochrome P450 2D6 was faster at pH 7.4. These results suggest that benzydamine N-oxygenation and N-demethylation are mediated by FMO1/3 and P450s, respectively, and that the contribution of FMO to metabolic eliminations of new drug candidates might be underestimated under certain experimental conditions suitable for P450 enzymes.
[Mh] Termos MeSH primário: Anti-Inflamatórios/metabolismo
Benzidamina/análogos & derivados
Sistema Enzimático do Citocromo P-450/metabolismo
Microssomos Hepáticos/metabolismo
Oxigenases/metabolismo
[Mh] Termos MeSH secundário: Animais
Benzidamina/metabolismo
Biotransformação
Sistema Enzimático do Citocromo P-450/genética
Cães
Seres Humanos
Técnicas In Vitro
Macaca fascicularis
Masculino
Metilação
Microssomos Hepáticos/enzimologia
Oxirredução
Oxigenases/genética
Ratos Sprague-Dawley
Proteínas Recombinantes
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Recombinant Proteins); 36504-71-9 (benzydamine N-oxide); 4O21U048EF (Benzydamine); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.13.- (Oxygenases); EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming))
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150312
[Lr] Data última revisão:
150312
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150312
[St] Status:MEDLINE



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