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[PMID]:29176315
[Au] Autor:Liu Q; Luo D; Yang T; Liao B; Li H; Wang KJ
[Ti] Título:Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction.
[So] Source:Cell Physiol Biochem;44(3):907-919, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. METHODS: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. RESULTS: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. CONCLUSION: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.
[Mh] Termos MeSH primário: Antagonistas Muscarínicos/farmacologia
Substâncias Protetoras/farmacologia
Bexiga Urinária/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Benzofuranos/farmacologia
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Colágeno/metabolismo
Citocinas/metabolismo
Modelos Animais de Doenças
Feminino
Seres Humanos
Imuno-Histoquímica
Contração Muscular/efeitos dos fármacos
Miócitos de Músculo Liso/citologia
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
Cloreto de Potássio/farmacologia
Antígeno Nuclear de Célula em Proliferação/metabolismo
Pirrolidinas/farmacologia
Ratos
Ratos Sprague-Dawley
Receptor Muscarínico M3/metabolismo
Tartarato de Tolterodina/farmacologia
Bexiga Urinária/metabolismo
Bexiga Urinária/patologia
Obstrução do Colo da Bexiga Urinária/metabolismo
Obstrução do Colo da Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzofurans); 0 (Cytokines); 0 (Muscarinic Antagonists); 0 (Proliferating Cell Nuclear Antigen); 0 (Protective Agents); 0 (Pyrrolidines); 0 (Receptor, Muscarinic M3); 5T619TQR3R (Tolterodine Tartrate); 660YQ98I10 (Potassium Chloride); 9007-34-5 (Collagen); APG9819VLM (darifenacin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485358


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[PMID]:28858835
[Au] Autor:Rajabalaya R; Mun CY; Chellian J; Chakravarthi S; David SR
[Ad] Endereço:.
[Ti] Título:Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro and in vivo evaluation.
[So] Source:Acta Pharm;67(3):325-339, 2017 Sep 01.
[Is] ISSN:1846-9558
[Cp] País de publicação:Croatia
[La] Idioma:eng
[Ab] Resumo:The purpose of the study was to develop a transdermal tolterodine tartrate (TT) patch and to analyse its efficacy for overactive bladder (OAB) treatment. Patches were prepared using various polymers and plasticizers via the solvent casting method. The patches were characterized for tensile strength, thickness, moisture content, modulus of elasticity and water absorption capacity. Differential scanning calorimetry and Fourier transform infrared analyses were also performed. To determine patch effectiveness, in vitro release, permeation and animal studies were performed. The patches showed satisfactory percentage of release, up to 89.9 %, and their mechanical properties included thickness (0.10-0.15 mm), tensile strength (4.62-9.98 MPa) and modulus of elasticity (20-29 MPa). There were no significant interactions between TT and other excipients. Animal studies indicated that the TT patch reduced the incidence of side effects; however, studies of longer duration are required to determine the effectiveness in treating OAB.
[Mh] Termos MeSH primário: Tartarato de Tolterodina/administração & dosagem
Adesivo Transdérmico
Bexiga Urinária Hiperativa/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Cutânea
Animais
Masculino
Ratos Sprague-Dawley
Absorção Cutânea
Tartarato de Tolterodina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5T619TQR3R (Tolterodine Tartrate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE


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[PMID]:28431780
[Au] Autor:Ananchenko G; Novakovic J
[Ad] Endereço:Apotex Inc., Toronto, ON, Canada.
[Ti] Título:Tolterodine Tartrate.
[So] Source:Profiles Drug Subst Excip Relat Methodol;42:339-403, 2017.
[Is] ISSN:1871-5125
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Tolterodine tartrate belongs to the family of muscarinic receptor antagonists and is indicated for the treatment of overactive urinary bladder syndrome. This chapter provides an overview of physical, analytical, and ADME profiles; highlights methods of chemical synthesis; and discusses stability of tolterodine as a free base and/or its l-tartrate salt in solution and in the solid state. The information presented in this chapter is based on the peer-reviewed literature, compendial reports (USP, EP), and authors' data. Patent literature is included only in a few instances.
[Mh] Termos MeSH primário: Antagonistas Muscarínicos
Tartarato de Tolterodina
[Mh] Termos MeSH secundário: Estabilidade de Medicamentos
Seres Humanos
Antagonistas Muscarínicos/química
Antagonistas Muscarínicos/farmacocinética
Antagonistas Muscarínicos/farmacologia
Antagonistas Muscarínicos/uso terapêutico
Tartarato de Tolterodina/química
Tartarato de Tolterodina/farmacocinética
Tartarato de Tolterodina/farmacologia
Tartarato de Tolterodina/uso terapêutico
Bexiga Urinária Hiperativa/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Muscarinic Antagonists); 5T619TQR3R (Tolterodine Tartrate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170423
[St] Status:MEDLINE


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[PMID]:28199076
[Au] Autor:Zachariou A; Filiponi M
[Ad] Endereço:Department of Urology, Elpis Hospital, Volos, Greece.
[Ti] Título:The effect of extended release tolterodine used for overactive bladder treatment on female sexual function.
[So] Source:Int Braz J Urol;43(4):713-720, 2017 Jul-Aug.
[Is] ISSN:1677-6119
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Overactive bladder (OAB) is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER) used for OAB treatment on the sexual function of women. MATERIALS AND METHODS: Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI) questionnaire. 73 patients of group A (control group) received no treatment and 85 patients of group B received an anticholinergic regimen - tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. RESULTS: A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment), arousal (3.1±0.2 to 3.1±0.2 respectively), lubrication (3.4±0.3 to 4.3±0.3 respectively), orgasm (3.5±0.3 to 4.5±0.3 respectively), satisfaction (2.6±0.2 to 4.2±0.3 respectively) and pain (2.4±0.2 to 4.6±0.4 respectively) after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05). Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5) compared to pre-treatment values (17.4±1.4, p<0.01) and to control group A (17.7±1.2 and 17.9±1.5, p>0,05) respectively. CONCLUSIONS: This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.
[Mh] Termos MeSH primário: Comportamento Sexual/efeitos dos fármacos
Disfunções Sexuais Fisiológicas/tratamento farmacológico
Tartarato de Tolterodina/uso terapêutico
Bexiga Urinária Hiperativa/tratamento farmacológico
Agentes Urológicos/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Preparações de Ação Retardada
Feminino
Seres Humanos
Meia-Idade
Estudos Prospectivos
Inquéritos e Questionários
Tartarato de Tolterodina/efeitos adversos
Agentes Urológicos/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Urological Agents); 5T619TQR3R (Tolterodine Tartrate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170216
[St] Status:MEDLINE


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[PMID]:28120444
[Au] Autor:Orgen S; Deliktas H; Sahin H; Gedik A; Nergis Y
[Ad] Endereço:Department of Urology, Batman State Hospital, Batman, Turkey.
[Ti] Título:Histopathologic and Urodynamic Effects of the Anticholinergic Drugs Oxybutynin, Tolterodine, and Trospium on the Bladder.
[So] Source:Low Urin Tract Symptoms;9(1):52-56, 2017 Jan.
[Is] ISSN:1757-5672
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: This study aimed to evaluate the effects of intravesical instillation of the anticholinergic drugs oxybutynin, tolterodine, and trospium on bladder capacity and histopathological changes in the bladder mucosa. METHODS: The study included 20 male New Zealand white rabbits that were randomly allocated to four groups of five. In the oxybutynin, tolterodine, and trospium groups, the drugs used were 1 mg/kg of crushed tablet mixed with 5 mL of saline, instilled intravesically once per day for 4 weeks. The control group was administered only 5 mL of saline once per day for 4 weeks. Urodynamic measurement of the bladder was made before and after treatment. At the end of the treatment the animals were killed and the bladders were evaluated histopathologically. RESULTS: There were no significant differences between pre- and post-treatment bladder capacity in any of the groups (P > 0.05). Histopathological evaluation showed that the mucosal epithelium was intact and there was minor inflammation in the control group and oxybutynin group (P > 0.05), whereas there was destruction of the mucosal epithelium and findings of diffuse inflammation in the tolterodine (P = 0.014) and trospium (P = 0.014) groups. CONCLUSION: Intravesical oxybutynin treatment was observed to be safe; however, a single daily dose of oxybutynin may not be sufficient to increase bladder capacity. Intravesical use of trospium and tolterodine at high doses caused epithelial destruction and diffuse inflammation in the bladder mucosa. The irritation associated with epithelial destruction and inflammation prevented an increase in bladder capacity.
[Mh] Termos MeSH primário: Benzilatos/farmacologia
Ácidos Mandélicos/farmacologia
Antagonistas Muscarínicos/farmacologia
Nortropanos/farmacologia
Tartarato de Tolterodina/farmacologia
Bexiga Urinária/efeitos dos fármacos
Agentes Urológicos/farmacologia
[Mh] Termos MeSH secundário: Animais
Masculino
Coelhos
Distribuição Aleatória
Urotélio/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzilates); 0 (Mandelic Acids); 0 (Muscarinic Antagonists); 0 (Nortropanes); 0 (Urological Agents); 1E6682427E (trospium chloride); 5T619TQR3R (Tolterodine Tartrate); K9P6MC7092 (oxybutynin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1111/luts.12096


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[PMID]:28087463
[Au] Autor:Wang H; Dai DP; Sun P; Xu LP; Liang BQ; Cai JP; Hu GX
[Ad] Endereço:Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
[Ti] Título:Effect of 22 CYP2D6 variants found in the Chinese population on tolterodine metabolism in vitro.
[So] Source:Chem Biol Interact;264:10-15, 2017 Feb 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Cytochrome P450 2D6 (CYP2D6) is an important member of the cytochrome P450 enzyme superfamily. We recently identified 22 novel variants in the Chinese population using PCR and bidirectional sequencing methods. The aim of this study is to characterize the enzymatic activity of these variants and their effects on the metabolism of the antimuscarinic drug tolterodine in vitro. A baculovirus-mediated expression system was used to express wild-type CYP2D6 and 24 variants (CYP2D6*2, CYP2D6*10, and 22 novel CYP2D6 variants) at high levels. The insect microsomes expressing CYP2D6 proteins were incubated with 0.1-50 µM tolterodine at 37 °C for 30 min and the metabolites were analyzed by high-performance liquid chromatography-tandem mass spectrometry system. Of the 24 CYP2D6 variants tested, 2 variants (CYP2D6*92 and CYP2D6*96) were found to be catalytically inactive, 4 variants (CYP2D6*94, F164L, F219S and D336N) exhibited markedly increased intrinsic clearance values (V /K ) compared with the wild-type (from 66.34 to 99.79%), whereas 4 variants (CYP2D6*10, *93, *95 and E215K) exhibited significantly decreased values (from 49.02 to 98.50%). This is the first report of all these rare alleles for tolterodine metabolism and these findings suggest that more attention should be paid to subjects carrying these infrequent CYP2D6 alleles when administering tolterodine in the clinic.
[Mh] Termos MeSH primário: Citocromo P-450 CYP2D6/genética
Citocromo P-450 CYP2D6/metabolismo
Antagonistas Muscarínicos/metabolismo
Polimorfismo Genético
Tartarato de Tolterodina/metabolismo
[Mh] Termos MeSH secundário: Alelos
Animais
Grupo com Ancestrais do Continente Asiático/genética
China
Citocromo P-450 CYP2D6/química
Seres Humanos
Insetos
Microssomos/metabolismo
Modelos Moleculares
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Muscarinic Antagonists); 5T619TQR3R (Tolterodine Tartrate); EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE


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[PMID]:27678410
[Au] Autor:Doricakova A; Theile D; Weiss J; Vrzal R
[Ad] Endereço:Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71, Olomouc, Czech Republic.
[Ti] Título:Differential effects of the enantiomers of tamsulosin and tolterodine on P-glycoprotein and cytochrome P450 3A4.
[So] Source:Naunyn Schmiedebergs Arch Pharmacol;390(1):49-59, 2017 Jan.
[Is] ISSN:1432-1912
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The pregnane X receptor (PXR) is a transcription factor regulating P-glycoprotein (P-gp; ABCB1)-mediated transport and cytochrome P450 3A4 (CYP3A4)-mediated metabolism of xenobiotics thereby affecting the pharmacokinetics of many drugs and potentially modulating clinical efficacy. Thus, pharmacokinetic drug-drug interactions can arise from PXR activation. Here, we examined whether the selective α1-adrenoreceptor blocker tamsulosin or the antagonist of muscarinic receptors tolterodine affect PXR-mediated regulation of CYP3A4 and of P-gp at the messenger RNA (mRNA) and protein level in an enantiomer-specific way. In addition, the effect of tamsulosin and tolterodine on P-gp activity was evaluated. We used quantitative real-time PCR, gene reporter assay, western blotting, rhodamine efflux assay, and calcein assay for determination of expression, activity, and inhibition of P-glycoprotein. The studied compounds significantly and concentration-dependently increased PXR activity in the ABCB1-driven luciferase-based reporter gene assay. We observed much stronger induction of ABCB1 mRNA by S-tamsulosin as compared to the R or racemic form. R or racemic form of tolterodine and R-tamsulosin concentration-dependently increased P-gp protein expression; the latter also enhanced P-gp efflux function in a rhodamine-based efflux assay. R-tamsulosin and all forms of tolderodine slightly inhibited P-gp. The effect on CYP3A4 expression followed the same pattern but was much weaker. Taken together, tamsulosin and tolterodine are demonstrated to interfere with P-gp and CYP3A4 regulation in an enantiomer-specific way.
[Mh] Termos MeSH primário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Citocromo P-450 CYP3A/metabolismo
Sulfonamidas/farmacologia
Tartarato de Tolterodina/farmacologia
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Animais
Linhagem Celular Tumoral
Citocromo P-450 CYP3A/genética
Relação Dose-Resposta a Droga
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Isomerismo
Células LLC-PK1
Camundongos
Regiões Promotoras Genéticas
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Receptores de Esteroides/agonistas
Receptores de Esteroides/metabolismo
Relação Estrutura-Atividade
Sulfonamidas/química
Suínos
Tartarato de Tolterodina/química
Transfecção
Regulação para Cima
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (P-glycoprotein 2); 0 (RNA, Messenger); 0 (Receptors, Steroid); 0 (Sulfonamides); 0 (multidrug resistance protein 3); 0 (pregnane X receptor); 5T619TQR3R (Tolterodine Tartrate); EC 1.14.13.67 (CYP3A4 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP3A); EC 1.14.14.1 (cytochrome P450 3A4, mouse); G3P28OML5I (tamsulosin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160929
[St] Status:MEDLINE
[do] DOI:10.1007/s00210-016-1304-9


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[PMID]:27087507
[Au] Autor:Leng J; Liao L; Wan B; Du C; Li W; Xie K; Shen Z; Xu Z; Wu S; Fang Z; Ma L; Han S; Feustel C; Yang Y; Madersbacher H
[Ad] Endereço:Renji Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China.
[Ti] Título:Results of a randomized, double-blind, active-controlled clinical trial with propiverine extended release 30 mg in patients with overactive bladder.
[So] Source:BJU Int;119(1):148-157, 2017 Jan.
[Is] ISSN:1464-410X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg ER formulation of tolterodine tartrate in patients with overactive bladder (OAB) in a non-inferiority trial. PATIENTS AND METHODS: Eligible patients, aged 18-75 years and with symptoms of OAB, were enrolled in this multicentre, randomized, double-blind, parallel-group, active-controlled study. After a 2-week screening period, patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8-week treatment period. Efficacy was assessed using a 3-day voiding diary and patient's self-reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post-void residual urine and electrocardiograms. RESULTS: A total of 324 patients (244 female and 80 male) were included in the study. Both active treatments improved the variables included in the voiding diary and in the patient's self-reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared with the tolterodine ER 4 mg group after 8 weeks of treatment (full analysis set [FAS] -4.6 ± 4.1 vs -3.8 ± 5.1; P = 0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (P = 0.026) and 8 weeks (P = 0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated, with a similar frequency of adverse drug reactions in both the propiverine ER 30 mg and tolterodine ER 4 mg groups (FAS 40.7 vs 39.5%; P = 0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment because of adverse drug reactions compared with propiverine ER 30 mg (7.4 vs 3.1%). CONCLUSIONS: Propiverine ER 30 mg was confirmed to be an effective and well-tolerated treatment option for patients with OAB symptoms. This first head-to-head study showed non-inferiority of propiverine ER 30 mg compared with tolterodine ER 4 mg.
[Mh] Termos MeSH primário: Benzilatos/administração & dosagem
Antagonistas Muscarínicos/administração & dosagem
Tartarato de Tolterodina/administração & dosagem
Bexiga Urinária Hiperativa/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Preparações de Ação Retardada
Método Duplo-Cego
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Benzilates); 0 (Delayed-Action Preparations); 0 (Muscarinic Antagonists); 468GE2241L (propiverine); 5T619TQR3R (Tolterodine Tartrate)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170524
[Lr] Data última revisão:
170524
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160419
[St] Status:MEDLINE
[do] DOI:10.1111/bju.13500


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[PMID]:27958220
[Au] Autor:Cai JL; Zhou Z; Yang Y; Yan YF; Jing S; Na YQ
[Ad] Endereço:Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
[Ti] Título:Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size: A Double-blind, Placebo-controlled, Randomized Clinical Trial.
[So] Source:Chin Med J (Engl);129(24):2899-2906, 2016 12 20.
[Is] ISSN:0366-6999
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release (ER) with or without tamsulosin in patients with benign prostate hyperplasia (BPH) and larger prostate size. METHODS: Totally, 152 patients (age ≥50 years) with BPH, International Prostate Symptom Score (IPSS) ≥12, quality-of-life (QoL) score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups (n = 38 in each) to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS (total, storage, and voiding subscales), QoL, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) were collected at baseline, and at weeks 4, 12, and 24. RESULTS: Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS (-7.15, -12.20, and -14.66 vs. -3.51, -5.78, and -7.23), storage IPSS (-3.56, -5.63, and -6.66 vs. -1.52, -1.21, and -2.43), voiding IPSS (-2.88, -5.10, and -6.48 vs. -1.52, -3.03, and -2.97), QoL (-1.21, -2.40, and -3.21 vs. -0.39, -1.41, and -1.60), Qmax (2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s), and PVR (-17.88, -26.97, and -27.89 ml vs. -12.03, -11.16, and -16.73 ml) at weeks 4, 12, and 24, respectively; the differences were all statistically significant (P < 0.05). Adverse events (AEs) were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS (-4.61, -6.79, and -5.70), voiding IPSS (-0.64, -1.83, and -1.45), QoL (-0.69, -1.21, and -1.41), or Qmax(-0.79, 2.83, and 1.11 ml/s), compared with placebo (all P > 0.05). However, a gradual increase in PVR (10.03, 10.41, and 12.89 ml) and more urinary AEs suggestive of urinary retention (11/38 vs. 4/38) were observed. CONCLUSION: Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume. TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR-TRC-09000596; http://www.chictr.org.cn/showproj.aspx?proj=8939.
[Mh] Termos MeSH primário: Hiperplasia Prostática/tratamento farmacológico
Sulfonamidas/uso terapêutico
Tartarato de Tolterodina/uso terapêutico
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos alfa/administração & dosagem
Antagonistas Adrenérgicos alfa/uso terapêutico
Idoso
Método Duplo-Cego
Esquema de Medicação
Feminino
Seres Humanos
Masculino
Meia-Idade
Próstata/efeitos dos fármacos
Próstata/patologia
Qualidade de Vida
Sulfonamidas/administração & dosagem
Tartarato de Tolterodina/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic alpha-Antagonists); 0 (Sulfonamides); 5T619TQR3R (Tolterodine Tartrate); G3P28OML5I (tamsulosin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170323
[Lr] Data última revisão:
170323
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE
[do] DOI:10.4103/0366-6999.195461


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[PMID]:27829538
[Au] Autor:Nomura Y; Iitsuka H; Toyoshima J; Kuroishi K; Hatta T; Kaibara A; Katashima M; Moy S; Sawamoto T
[Ad] Endereço:Clinical Pharmacology, Development, Astellas Pharma Inc., 2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo 103-8411, Japan. Electronic address: yuki.nomura@astellas.com.
[Ti] Título:Pharmacokinetic drug interaction study between overactive bladder drugs mirabegron and tolterodine in Japanese healthy postmenopausal females.
[So] Source:Drug Metab Pharmacokinet;31(6):411-416, 2016 Dec.
[Is] ISSN:1880-0920
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mirabegron, the first selective ß -adrenoceptor agonist for the treatment of overactive bladder (OAB), inhibits cytochrome P450 isozyme CYP2D6. This study was performed in Japanese healthy postmenopausal female volunteers to assess any pharmacokinetic drug interaction between mirabegron and tolterodine, another OAB drug and a sensitive substrate of CYP2D6. Tolterodine 4 mg was orally administered from Days 1-7 and co-administered with mirabegron 50 mg from Days 8-14. Mirabegron 50 mg increased maximum concentration (C ) and area under the concentration-time curve from zero to 24 h after dosing (AUC ) of tolterodine by 2.06-fold (90% confidence interval [CI] 1.81, 2.34) and 1.86-fold (90% CI 1.60, 2.16), respectively, and increased C and AUC of the metabolite 5-hydroxymethyl tolterodine by 1.36-fold (90% CI 1.26, 1.47) and 1.25-fold (90% CI 1.15, 1.37), respectively. This suggested a weak pharmacokinetic drug interaction between mirabegron and tolterodine. Mean change from baseline of Fridericia's QT correction formula (ΔQTcF) was slightly higher on Day 14 than on Day 7. No subject had QTcF >480 msec or ΔQTcF >60 msec. All the treatment-emergent adverse events were mild. Mirabegron 50 mg was considered to be safe and well tolerated when coadministered with tolterodine 4 mg in healthy postmenopausal female volunteers.
[Mh] Termos MeSH primário: Acetanilidas/farmacologia
Agonistas de Receptores Adrenérgicos beta 3/farmacologia
Tiazóis/farmacologia
Tartarato de Tolterodina/farmacocinética
Agentes Urológicos/farmacocinética
[Mh] Termos MeSH secundário: Acetanilidas/efeitos adversos
Acetanilidas/farmacocinética
Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos
Agonistas de Receptores Adrenérgicos beta 3/farmacocinética
Compostos Benzidrílicos/farmacocinética
Cresóis/farmacocinética
Interações Medicamentosas
Feminino
Voluntários Saudáveis
Seres Humanos
Meia-Idade
Pós-Menopausa
Tiazóis/efeitos adversos
Tiazóis/farmacocinética
Tartarato de Tolterodina/efeitos adversos
Agentes Urológicos/efeitos adversos
Agentes Urológicos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-hydroxymethyl tolterodine); 0 (Acetanilides); 0 (Adrenergic beta-3 Receptor Agonists); 0 (Benzhydryl Compounds); 0 (Cresols); 0 (Thiazoles); 0 (Urological Agents); 5T619TQR3R (Tolterodine Tartrate); MVR3JL3B2V (mirabegron)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170317
[Lr] Data última revisão:
170317
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161111
[St] Status:MEDLINE



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