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1.
Br J Cancer ; 116(12): 1505-1512, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463960

RESUMO

BACKGROUND: To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). METHODS: Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. RESULTS: Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). CONCLUSIONS: Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Transdução de Sinais/genética , Sulfóxidos/administração & dosagem , Sulfóxidos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacocinética , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/farmacocinética , Diarreia/induzido quimicamente , Fadiga/induzido quimicamente , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfoma/tratamento farmacológico , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/genética , Neoplasias Ovarianas/tratamento farmacológico , Antígeno Nuclear de Célula em Proliferação/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Vômito/induzido quimicamente
2.
J Dig Dis ; 13(2): 113-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22257480

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effects and safety of different doses of ilaprazole on healthy volunteers without a Helicobacter pylori infection. METHODS: A total of 12 healthy Chinese volunteers were enrolled and divided into four groups randomly, with a 5-day treatment of oral ilaprazole 5mg, 10mg and 20mg or omeprazole 20mg, respectively. After an interval of a 14-day washout phase, each was switched to another dose group and eventually completed all four regimens. The percentage time of intragastric pH>4 was the major index. The polymorphisms of the metabolic enzyme CYP2C19 in these volunteers were also detected. RESULTS: The percentage time of intragastric pH>4 in the ilaprazole 5, 10 and 20mg groups were 80.4%, 88.1% and 91.0%, respectively, during the first 24h, compared to that of the 20mg omeprazole group (76.6%, P>0.05). Ilaprazole 20mg provided a significant higher mean 24-h pH than that of the same dose of omeprazole both on Day 1 (7.78 vs 6.67, P<0.01) and Day 5 (7.95 vs 7.44, P<0.05). No CYP2C19-dependent difference or obvious adverse effect were found in any ilaprazole groups. CONCLUSION: Low dose ilaprazole offers a gastric acid inhibition comparable to a routine dose of omeprazole, and further investigations in patients with acid-associated diseases are needed.


Assuntos
Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Ácido Gástrico/metabolismo , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Inibidores da Bomba de Prótons , Estômago/efeitos dos fármacos , Sulfóxidos/administração & dosagem , Sulfóxidos/efeitos adversos , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Hidrocarboneto de Aril Hidroxilases/genética , Estudos Cross-Over , Citocromo P-450 CYP2C19 , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Feminino , Determinação da Acidez Gástrica , Helicobacter pylori , Humanos , Masculino , Omeprazol/administração & dosagem , Polimorfismo Genético , Valores de Referência , Adulto Jovem
3.
Curr Med Res Opin ; 28(1): 101-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22070512

RESUMO

OBJECTIVE: The new proton pump inhibitor (PPI), ilaprazole performed better at the dose of 10 mg/d relative to 5 or 20 mg/d in a previous phase II trial. A larger phase III trial was carried out to confirm the efficacy and safety of ilaprazole (10 mg/d) compared with omeprazole (20 mg/d) and provide some characteristics of the relationship between ilaprazole metabolism and CYP2C19 for later studies. RESEARCH DESIGN AND METHODS: Patients with at least one endoscopically diagnosed active duodenal ulcer (DU) were enrolled in a multicenter, randomized, double-blind, positive controlled trial and then assigned randomly to the ilaprazole group (10 mg/d) or the omeprazole group (20 mg/d) with a sample allocation ratio 2:1. The course of treatment was 4 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT00952978. MAIN OUTCOME MEASURES: The primary endpoint was endoscopically diagnosed ulcer healing rate at week 4. Symptom relief was evaluated as a secondary endpoint by graded scores. Safety and tolerability were evaluated on basis of clinical assessments. In addition, blood samples were collected at baseline for CYP2C19 genotypes identification. RESULTS: Efficacy analyses were based on 494 patients. At week 4, the ulcer healing rates were 93.0% in ilaprazole group and 90.8% in omeprazole group (rate difference: 2.2%; 95% confidence interval: -2.8% to 7.2%). No obvious variation of healing rate on different CYP2C19 genotypes was found in ilaprazole group. The majority of patients (>80%) became asymptomatic after treatment. Incidences of adverse drug reactions were similar between ilaprazole group and omeprazole group (8.5% vs. 11.5%). CONCLUSIONS: Ilaprazole (10 mg/d) is as effective as omeprazole (20 mg/d) in the treatment of DU with similar side effects. The efficacy of ilaprazole is not affected by CYP2C19 polymorphisms.


Assuntos
Benzimidazóis/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Adolescente , Adulto , Idoso , Antiulcerosos/efeitos adversos , Antiulcerosos/uso terapêutico , Hidrocarboneto de Aril Hidroxilases/genética , Benzimidazóis/efeitos adversos , Citocromo P-450 CYP2C19 , Método Duplo-Cego , Úlcera Duodenal/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Polimorfismo Genético/fisiologia , Sulfóxidos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
4.
J Clin Gastroenterol ; 45(4): 322-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20679904

RESUMO

GOALS: To investigate the efficacy and safety of a new proton pump inhibitor (PPI), ilaprazole (IY-81149) in the treatment of duodenal ulcers and provide some characteristics of the dose-response relationship for later studies. BACKGROUND: PPIs have been used therapeutically for many years, and shown great efficacy in accelerating ulcer healing. Currently researches are focused on more potent PPIs. Some preclinical studies have shown that ilaprazole might be such a new substitute. STUDY: 235 patients with at least 1 endoscopically diagnosed active duodenal ulcer were enrolled in a randomized trial. Patients were randomized into 4 groups (5, 10, and 20 mg/d ilaprazole, with 20 mg/d omeprazole as positive control) and treated for up to 4 weeks. Forty patients accepted continuous 24-hour pH measurements after the fifth dose. The primary endpoint was ulcer healing rate at week 4. RESULTS: The efficacy analyses were based on 235 patients. At week 4, 86.4%, 93.1%, 86.4%, and 89.8% patients treated with 5 mg ilaprazole, 10 mg ilaprazole, 20 mg ilaprazole, and 20 mg omeprazole once daily, respectively had ulcers healed (P=0.59). The majority of patients (>70%) became asymptomatic after 4 weeks treatment. Both drugs with stipulated dosages exhibited similar efficacy and safety profiles. Gastric acid suppression increased with increasing dose of ilaprazole in pH study. CONCLUSIONS: Ilaprazole is as tolerable, safe, and efficacious as omeprazole in the treatment of duodenal ulcers, especially at a lower dose (10 mg/d ilaprazole vs. 20 mg/d omeprazole). (ClinicalTrials.gov ID: NCT00953381).


Assuntos
Antiulcerosos/uso terapêutico , Benzimidazóis/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons , Inibidores da Bomba de Prótons/uso terapêutico , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Antiulcerosos/administração & dosagem , Antiulcerosos/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Sulfóxidos/administração & dosagem , Sulfóxidos/efeitos adversos , Resultado do Tratamento
5.
J Gastroenterol ; 44(7): 697-707, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19434360

RESUMO

PURPOSE: Ilaprazole (IY-81149) is a new proton-pump inhibitor (PPI) not previously studied in human patients with ulcer disease. This study evaluated and compared it with a reference PPI, omeprazole, in the treatment of gastric and duodenal ulcers. METHODS: This was a double-blind, parallel, randomized study. Patients aged 18 years and above with at least one endoscopically confirmed active non-malignant gastric/duodenal ulcer were treated with 20 mg/day omeprazole or 5 mg/day or 10 mg/day ilaprazole for four weeks. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated using a graded score. Safety and tolerability were evaluated on basis of clinical assessments. Between-group differences were tested using ANOVA or ANCOVA, as appropriate. Statistical significance was assumed at a two-tailed p value of 90%) became asymptomatic after treatment. At the dosages administered, both drugs exhibited similar efficacy and a similar safety profile. CONCLUSIONS: Ilaprazole is as tolerable, safe, and efficacious as omeprazole in the treatment of gastroduodenal ulcers, at a much lower dose (5 vs. 20 mg omeprazole).


Assuntos
Antiulcerosos/administração & dosagem , Benzimidazóis/administração & dosagem , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Sulfóxidos/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis , Benzimidazóis/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Úlcera Duodenal/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Úlcera Gástrica/tratamento farmacológico , Sulfóxidos/efeitos adversos
6.
Coll Antropol ; 30(3): 519-22, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17058517

RESUMO

The aim of this study was to compare the efficacy of esomeprazole and pantoprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. I this multicentre, randomized, single-blind study 180 patients (ITT population) diagnosed with endoscopically proven GERD grade A,B,C received esomeprazole (40 mg once daily (o.d.), n = 90) orpantoprazole (40 mg o.d., n = 90). Healing and relief from GERD-related symptoms were assessed at first and final visit (after 4 or 8 weeks of treatment). Esomeprazole 40 mg provided significantly greater healing than pantoprazole 40 mg after 4 weeks of treatment in patients with EE (77.8% vs. 72.2%). Esomeprazole-treated patients were healed after up to 8 weeks of treatment similar those treated with pantoprazole (92.2% vs. 91.1%). The proportion of heartburn-free days was similar in patients treated with esomeprazole and to those treated with pantoprazole.


Assuntos
Antiulcerosos/uso terapêutico , Benzimidazóis/uso terapêutico , Esomeprazol/análogos & derivados , Esomeprazol/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Idoso , Antiulcerosos/efeitos adversos , Benzimidazóis/efeitos adversos , Esomeprazol/efeitos adversos , Feminino , Refluxo Gastroesofágico/classificação , Refluxo Gastroesofágico/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol , Índice de Gravidade de Doença , Sulfóxidos/efeitos adversos , Resultado do Tratamento
8.
Dig Dis Sci ; 51(9): 1595-601, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16927137

RESUMO

We sought to evaluate safety and efficacy of IV pantoprazole when used as initial therapy in patients with gastroesophageal reflux disease (GERD) and a history of erosive esophagitis (EE) in a double-blind, placebo-controlled, randomized, parallel-group study. Patients were randomized to 7 days of once-daily IV or oral pantoprazole (40 mg) or placebo. Efficacy variables included maximal acid output, basal acid output, and changes from baseline in frequency/severity of GERD symptoms, and frequency of antacid usage. Seventy-eight patients were randomized (n=26/27/25 [IV/oral/placebo]). Mean maximal acid output was 8.4, 6.3, and 20.9 mEq/h for IV or oral pantoprazole, and placebo, respectively. For pantoprazole versus placebo, maximal and basal acid output were significantly lower (P<.001) and there was a numerical trend toward improved GERD and antacid usage. Both treatments were well tolerated. In conclusion, IV/oral pantoprazole were similarly effective in suppressing basal and pentagastrin-stimulated gastric acid secretion in GERD patients with a history of EE.


Assuntos
Antiulcerosos/administração & dosagem , Benzimidazóis/administração & dosagem , Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/análogos & derivados , Sulfóxidos/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis , Administração Oral , Adulto , Hidróxido de Alumínio/uso terapêutico , Análise de Variância , Antiulcerosos/efeitos adversos , Benzimidazóis/efeitos adversos , Pesos e Medidas Corporais , Método Duplo-Cego , Combinação de Medicamentos , Esofagite Péptica/etiologia , Feminino , Ácido Gástrico/fisiologia , Determinação da Acidez Gástrica , Refluxo Gastroesofágico/complicações , Humanos , Infusões Intravenosas , Hidróxido de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Pantoprazol , Efeito Placebo , Índice de Gravidade de Doença , Ácido Silícico/uso terapêutico , Sulfóxidos/efeitos adversos , Resultado do Tratamento
9.
Clin Ther ; 28(5): 725-33, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16861094

RESUMO

BACKGROUND: After a course of IV proton pump inhibitor therapy, patients might require continued oral antisecretory therapy. A direct comparison of therapeutic alternatives could assist physicians in decisions regarding optimal acid-suppressive therapy. Oral esomeprazole might control intragastric acidity more effectively compared with other acid-suppressive agents after IV therapy. OBJECTIVE: The aim of this study was to compare intragastric acid control on day 5 of administration of esomeprazole magnesium versus pantoprazole 40 mg PO QD after switching from 5 days of treatment with pantoprazole 40 mg IV in healthy volunteers. METHODS: This randomized, open-label, comparative, 2-way crossover study was conducted at the Oklahoma Foundation for Digestive Research, Oklahoma City, Oklahoma, between October and December 2004. Healthy, Helicobacter pylori-negative adults were randomly assigned to 1 of 2 dosing sequences: pantoprazole IV followed by esomeprazole PO or pantoprazole IV followed by pantoprazole PO. All study medications were administered for 5 days at a dose of 40 mg QD. IV pantoprazole was administered over 2 minutes; all medications were administered 30 minutes before breakfast. There was a 10- to 21-day washout period between each 10-day dosing period. All doses were administered at the study site. Before oral study drug administration on days 1 and 5, 24-hour pH monitoring was performed using a pH catheter positioned 10 cm distal to the lower esophageal sphincter in the stomach. The primary end point was percentage of time with pH >4 (%t pH >4) during the 24-hour pH-monitoring period. Tolerability was assessed using spontaneous reporting, laboratory analysis, and vital-sign measurement. RESULTS: Of 42 subjects randomized to treatment sequences, 4 were withdrawn during the study because of invalid pH data; 38 subjects (24 men, 14 women; mean [SD] age, 25.2 [8.1] years) had assessable data. Day-5 %t pH >4 was 68.5% with esomeprazole and 53.3% with pantoprazole (P < 0.001). Day-1 %t pH >4 was 62.5% with esomeprazole and 51.0% with pantoprazole (P < 0.001). The most common adverse events were rhinitis (2 subjects each with pantoprazole IV and PO; 1 subject with esomeprazole) and headache (2 subjects with esomeprazole; 1 subject with pantoprazole IV). CONCLUSIONS: The results of this study in healthy adult volunteers suggest that switching from pantoprazole 40 mg IV to esomeprazole 40 mg PO QD more effectively suppresses intragastric acid compared with switching from pantoprazole 40 mg IV to pantoprazole 40 mg PO QD. All 3 treatments were well tolerated.


Assuntos
Antiulcerosos/farmacologia , Benzimidazóis/farmacologia , Inibidores Enzimáticos/farmacologia , Esomeprazol/análogos & derivados , Esomeprazol/administração & dosagem , Esomeprazol/farmacologia , Ácido Gástrico/metabolismo , Inibidores da Bomba de Prótons , Sulfóxidos/farmacologia , 2-Piridinilmetilsulfinilbenzimidazóis , Administração Oral , Adulto , Algoritmos , Antiulcerosos/efeitos adversos , Benzimidazóis/efeitos adversos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/efeitos adversos , Esomeprazol/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Oklahoma , Pantoprazol , Sulfóxidos/efeitos adversos , Fatores de Tempo
11.
Z Gastroenterol ; 44(5): 379-85, 2006 May.
Artigo em Alemão | MEDLINE | ID: mdl-16688654

RESUMO

AIMS: To directly compare the efficacy and safety of pantoprazole 40 mg VS. omeprazole 20 mg in patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: 915 Patients suffering from symptomatic GERD B-D (Los Angeles classification) were included in a double-blind randomized multicenter clinical trial and treated with either pantoprazole 40 mg od or omeprazole 20 mg od for six weeks. Primary efficacy criterion was the first time to reach normal symptoms as assessed by the questionnaire ReQuest-GI. RESULTS: Compared to omeprazole 20 mg, pantoprazole 40 mg achieved a significantly faster rate of symptom relief (p = 0.0298). Thus, as assessed with the ReQuest questionnaire, patients treated with pantoprazole 40 mg experienced relief from the 7 leading GERD symptoms 2 days earlier than those treated with omeprazole 20 mg. Long-lasting sustained relief from symptoms was also achieved earlier with pantoprazole than with omeprazole; in patients treated with pantoprazole, the daily symptom load was lower than in those treated with omeprazole. After 6 weeks of treatment, over 90 percent of patients were free from symptoms in both treatment groups (93.7 % in the pantoprazole, vs. 91.8 % in the omeprazole group, PP). Both medications were well tolerated. CONCLUSIONS: GERD patients treated with pantoprazole 40 mg experience a significantly faster relief from their leading symptoms than those treated with omeprazole 20 mg.


Assuntos
Antiulcerosos/economia , Antiulcerosos/uso terapêutico , Benzimidazóis/economia , Benzimidazóis/uso terapêutico , Controle de Custos/economia , Custos de Medicamentos/estatística & dados numéricos , Esofagite Péptica/economia , Programas Nacionais de Saúde/economia , Omeprazol/análogos & derivados , Omeprazol/economia , Omeprazol/uso terapêutico , Qualidade da Assistência à Saúde/economia , Sulfóxidos/economia , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Antiulcerosos/efeitos adversos , Benzimidazóis/efeitos adversos , Relação Dose-Resposta a Droga , Esofagite Péptica/diagnóstico , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/psicologia , Feminino , Alemanha , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Medição da Dor , Pantoprazol , Qualidade de Vida/psicologia , Papel do Doente , Sulfóxidos/efeitos adversos , Resultado do Tratamento
12.
Aliment Pharmacol Ther ; 23(7): 985-95, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16573801

RESUMO

BACKGROUND: Orally and intravenously administered proton pump inhibitors have been shown to reduce rebleeding rates, surgery and transfusion requirement. AIM: To compare lansoprazole intravenous and orally disintegrating tablet (Prevacid SoluTab) regimens with a pantoprazole intravenously administered regimen in sustaining intragastric pH >6.0. METHODS: Two similarly designed three-way, randomized crossover studies each enrolled 36 Helicobacter pylori-negative healthy volunteers. Study 1 regimens included intravenously administered bolus followed by 24-h continuous infusion (lansoprazole 90 mg, 6 mg/h; lansoprazole 120 mg, 6 mg/h; pantoprazole 80 mg, 8 mg/h). Study 2 regimens included intravenous bolus followed by lansoprazole orally disintegrating tablet or intravenous continuous infusion for 24 h (lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg every 6 h; lansoprazole 120 mg, 9 mg/h; pantoprazole 80 mg, 8 mg/h). Percentage of time pH >6.0 was assessed with 24-h intragastric pH monitoring. RESULTS: All regimens produced comparable gastric acid suppression. In both studies, regimens superior to pantoprazole included lansoprazole 90 mg, 6-mg/h; lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg q.d.s. and lansoprazole 120 mg, 9 mg/h (P < or = 0.013). The lansoprazole 120-mg, 6-mg/h regimen (P = 0.082) was not superior to pantoprazole in percentage of time intragastric pH >6.0. Mild reaction at the intravenous injection site was the most frequently reported adverse event. CONCLUSIONS: The intravenous bolus and continuously infused lansoprazole or intravenous bolus and intermittent lansoprazole orally disintegrating tablet regimens are as effective as intravenous pantoprazole in sustaining intragastric pH >6.0.


Assuntos
Antiulcerosos/administração & dosagem , Omeprazol/análogos & derivados , 2-Piridinilmetilsulfinilbenzimidazóis , Administração Oral , Adolescente , Adulto , Antiulcerosos/efeitos adversos , Antiulcerosos/farmacocinética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Benzimidazóis/farmacocinética , Estudos Cross-Over , Citocromo P-450 CYP2C19 , Relação Dose-Resposta a Droga , Feminino , Determinação da Acidez Gástrica , Genótipo , Humanos , Concentração de Íons de Hidrogênio , Infusões Intravenosas , Lansoprazol , Masculino , Taxa de Depuração Metabólica/fisiologia , Pessoa de Meia-Idade , Oxigenases de Função Mista/metabolismo , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Omeprazol/farmacocinética , Pantoprazol , Sulfóxidos/administração & dosagem , Sulfóxidos/efeitos adversos , Sulfóxidos/farmacocinética , Comprimidos
13.
Clin Gastroenterol Hepatol ; 4(5): 597-604, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16630752

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, and their usage worldwide is increasing. Although well-tolerated, there have been case reports and a recent case series implicating these drugs in acute interstitial nephritis (AIN) and progression to acute renal failure (ARF). The aim of this study was to investigate how widespread this complication is in Australia, to identify which PPIs are implicated, and to establish whether PPI-induced AIN is a class effect. METHODS: We undertook a retrospective case review of potential cases at 2 teaching hospitals and a review of registry data from the Therapeutic Goods Administration of Australia (TGA). Parameters sought included the drug implicated, concurrent medications, symptoms, signs, serum creatinine, and time of onset after prescription. RESULTS: We identified 18 cases of biopsy-proven PPI-induced AIN causing ARF in the retrospective case review, which is the largest hospital-based case series to date. The TGA registry data identified an additional 31 cases of "biopsy proven interstitial nephritis." An additional 10 cases of "suspected interstitial nephritis," 20 cases of "unclassified acute renal failure," and 26 cases of "renal impairment" were also identified. All 5 commercially available PPIs were implicated in these cases. CONCLUSION: With the ever more widespread use of this class of medications, PPI-induced AIN is likely to become more frequent. There is now evidence to incriminate all the commercially available PPIs, suggesting there is a class effect. Failure to recognize this entity might have catastrophic long-term consequences including chronic kidney disease. Increased awareness might facilitate more rapid diagnosis and management of this potentially reversible condition.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Inibidores Enzimáticos/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/epidemiologia , Inibidores da Bomba de Prótons , 2-Piridinilmetilsulfinilbenzimidazóis , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Austrália , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Dispepsia/diagnóstico , Dispepsia/tratamento farmacológico , Educação Médica Continuada , Inibidores Enzimáticos/uso terapêutico , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/patologia , Omeprazol/efeitos adversos , Omeprazol/análogos & derivados , Omeprazol/uso terapêutico , Pantoprazol , Prevalência , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Sulfóxidos/efeitos adversos , Sulfóxidos/uso terapêutico
14.
J Pediatr Gastroenterol Nutr ; 42(4): 384-91, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16641576

RESUMO

OBJECTIVE: To evaluate symptom improvement in 53 children (aged 5-11 years) with endoscopically proven gastroesophageal reflux disease (GERD) treated with pantoprazole (10, 20 and 40 mg) using the GERD Assessment of Symptoms in Pediatrics Questionnaire. METHODS: The GERD Assessment of Symptoms in Pediatrics Questionnaire was used to measure the frequency and severity over the previous 7 days of abdominal/belly pain, chest pain/heartburn, difficulty swallowing, nausea, vomiting/regurgitation, burping/belching, choking when eating and pain after eating. Individual symptom scores were based on the product of the frequency and usual severity of each symptom. The sum of the individual symptom score values made up the composite symptom score (CSS). The primary end point was the change in the mean CSS from baseline to week 8. RESULTS: Mean frequency and severity of each symptom significantly decreased (from P < 0.006 to P < 0.001) over time. Similar significant decreases in CSS at week 8 versus baseline (P < 0.001) were seen in all groups. Significant decreases from baseline in CSS were noted from weeks 1 to 8 in the 20-mg (P < 0.003) and 40-mg (P < 0.001) groups. The 20- and 40-mg doses were significantly (P < 0.05) more effective than the 10-mg dose in improving GERD symptoms at week 1. Adverse events were similar among the treatment groups. CONCLUSIONS: Pantoprazole (20 and 40 mg) is effective in reducing endoscopically proven GERD symptoms in children. Both 20 and 40 mg pantoprazole significantly reduced symptoms as early as 1 week.


Assuntos
Antiulcerosos/uso terapêutico , Benzimidazóis/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/patologia , Omeprazol/análogos & derivados , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Antiulcerosos/efeitos adversos , Benzimidazóis/efeitos adversos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Pantoprazol , Índice de Gravidade de Doença , Sulfóxidos/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
15.
Ann Pharmacother ; 40(4): 758-61, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16569810

RESUMO

OBJECTIVE: To report 2 cases of thrombocytopenia associated with pantoprazole treatment and discuss existing reports on this drug-induced adverse event. CASE SUMMARIES: This paper describes the course of thrombocytopenia associated with pantoprazole 40 mg in 2 hospitalized patients. In both cases, thrombocytopenia appeared after the initiation of pantoprazole and rapidly improved after discontinuation of pantoprazole, although complete resolution of thrombocytopenia occurred in only one patient prior to discharge from the hospital. DISCUSSION: The mechanism of drug-induced thrombocytopenia is often poorly understood, and proton-pump inhibitors are generally not strongly suspected as a cause of thrombocytopenia. However, an objective causality assessment using the Naranjo probability scale revealed a probable relationship between thrombocytopenia and pantoprazole in both of the cases. It is unknown whether this is a class effect. CONCLUSIONS: Although drug-induced thrombocytopenia with pantoprazole appears to be rare, it represents a potentially severe adverse effect. This supports the judicious prescribing of pantoprazole and possibly other proton-pump inhibitors.


Assuntos
Benzimidazóis/efeitos adversos , Omeprazol/análogos & derivados , Sulfóxidos/efeitos adversos , Trombocitopenia/induzido quimicamente , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Pantoprazol , Contagem de Plaquetas , Sulfóxidos/administração & dosagem , Sulfóxidos/uso terapêutico , Trombocitopenia/sangue
16.
J Rheumatol ; 33(3): 629-32, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16482642

RESUMO

Systemic vasculitis may, at times, be drug-induced and associated with antineutrophil cytoplasmic antibodies (ANCA). However, pantoprazole, a commonly used and well-tolerated proton pump inhibitor, has not previously been reported to cause ANCA-associated syndromes. We describe a patient who developed interstitial nephritis, cutaneous vasculitis, a perinuclear ANCA staining pattern (pANCA) on immunofluorescence, and anti-myeloperoxidase antibodies (MPO-ANCA) in association with pantoprazole. We review various immune-mediated syndromes reported in association with proton pump inhibitors, including one report of omeprazole associated with interstitial nephritis and the development of ANCA.


Assuntos
Antiulcerosos/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos/sangue , Benzimidazóis/efeitos adversos , Núcleo Celular/patologia , Omeprazol/análogos & derivados , Sulfóxidos/efeitos adversos , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , 2-Piridinilmetilsulfinilbenzimidazóis , Doença Aguda , Idoso , Núcleo Celular/imunologia , Doença Crônica , Exantema/induzido quimicamente , Exantema/imunologia , Exantema/terapia , Feminino , Humanos , Metilprednisolona/uso terapêutico , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/imunologia , Nefrite Intersticial/terapia , Omeprazol/efeitos adversos , Pantoprazol , Peroxidase/imunologia , Diálise Renal , Resultado do Tratamento , Vasculite Leucocitoclástica Cutânea/imunologia , Vasculite Leucocitoclástica Cutânea/terapia
17.
Aliment Pharmacol Ther ; 23(4): 481-8, 2006 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-16441468

RESUMO

BACKGROUND: Current 'rescue' therapies provide inadequate Helicobacter pylori eradication rates because of antibiotic resistance. AIM: To test the efficacy of a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as rescue therapy for patients in whom eradication of H. pylori had failed standard clarithromycin-based triple therapy. METHODS: One hundred and thirty patients (mean age 51.7 +/- 14.8 years) who had failed one or more eradication attempts with omeprazole, clarithromycin and amoxicillin were treated for 12 days with rifabutin 150 mg daily, amoxicillin 1 g or 1.5 g t.d.s, and pantoprazole 80 mg t.d.s. RESULTS: The intention-to-treat and per-protocol eradication rates were 90.8/90.8%. Metronidazole or/and clarithromycin resistance had no significant impact on H. pylori eradication rates. A higher overall eradication rate of 96.6% (95% CI: 92.1-101%) was obtained in patients treated with a regimen containing 1.5 g amoxicillin t.d.s compared with 90.7% (95% CI: 82-98.6%) using a regimen with 1 g amoxicillin t.d.s but the difference was not significant. Side-effects reported in 40% of patients were mild. CONCLUSION: A 12-day course of low dose of rifabutin with an increased dose of amoxicillin and pantoprazole is well-tolerated and highly effective against dual-resistant H. pylori infection after failure of triple therapy.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Rifabutina/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Antiulcerosos/administração & dosagem , Antiulcerosos/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Claritromicina/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metronidazol/administração & dosagem , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Omeprazol/análogos & derivados , Pantoprazol , Estudos Prospectivos , Rifabutina/efeitos adversos , Sulfóxidos/administração & dosagem , Sulfóxidos/efeitos adversos , Resultado do Tratamento
19.
Am J Gastroenterol ; 100(11): 2387-92, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16279889

RESUMO

OBJECTIVE: This prospective, randomized, controlled, head-to-head study was conducted to compare the efficacies of esomeprazole- and pantoprazole-based triple therapies for Helicobacter pylori eradication. METHODS: From January 2002 to October 2003, 200 H. pylori-infected patients were randomly assigned to undergo twice daily treatment with esomeprazole 40 mg (n = 100) or pantoprazole 40 mg (n = 100) combined with clarithromycin 500 mg and amoxicillin 1 g for 1 wk (ECA and PCA groups, respectively). Follow-up endoscopy was performed at 8 wks after the end of treatment to assess the treatment response. RESULTS: Intention-to-treat analysis demonstrated a significantly higher eradication rate for the ECA group than for the PCA group (94%vs 82%, respectively, p= 0.009). Per-protocol analysis also showed similar results (97%vs 84%, p= 0.003). Both groups had similar frequencies of adverse events (15%vs 24%) and drug compliance (97%vs 96%). Multivariate analysis disclosed that the use of esomeprazole (OR: 1.56, 95% CI, 1.11-2.19) and good compliance 7.39 (95% CI, 1.27-42.95) were independent predictors of treatment success. Alcohol drinking was an independent predictor of eradication failure (OR: 0.18; 95% CI, 0.06-0.54). CONCLUSION: Esomeprazole-based triple therapy demonstrated a higher eradication rate than pantoprazole-based regimen. The differences in eradiation efficacies between the two study groups may be related to the more powerful acid inhibition effect and stronger anti-H. pylori activity of esomeprazole compared to pantoprazole.


Assuntos
Antiulcerosos/uso terapêutico , Benzimidazóis/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Esomeprazol/análogos & derivados , Esomeprazol/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Consumo de Bebidas Alcoólicas , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Antiulcerosos/efeitos adversos , Benzimidazóis/efeitos adversos , Claritromicina/efeitos adversos , Claritromicina/uso terapêutico , Quimioterapia Combinada , Inibidores Enzimáticos/efeitos adversos , Esomeprazol/efeitos adversos , Feminino , Seguimentos , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol , Cooperação do Paciente , Úlcera Péptica/microbiologia , Projetos Piloto , Estudos Prospectivos , Sulfóxidos/efeitos adversos , Resultado do Tratamento
20.
Aliment Pharmacol Ther ; 22(9): 803-11, 2005 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16225489

RESUMO

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.


Assuntos
Benzimidazóis/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Esomeprazol/análogos & derivados , Esomeprazol/uso terapêutico , Esofagite Péptica/prevenção & controle , Sulfóxidos/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Antiulcerosos/efeitos adversos , Antiulcerosos/uso terapêutico , Benzimidazóis/efeitos adversos , Método Duplo-Cego , Tolerância a Medicamentos , Inibidores Enzimáticos/efeitos adversos , Esomeprazol/efeitos adversos , Esofagite Péptica/etiologia , Esofagoscopia , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol , Inibidores da Bomba de Prótons , Prevenção Secundária , Sulfóxidos/efeitos adversos , Resultado do Tratamento
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