RESUMEN
The drug delivery systems are an important strategy of pharmaceutical technology to modulate undesirable properties, increasing efficacy, and reducing the side effects of active pharmaceutical ingredients (API). The sustained release is a type of controlled-release system that provides a suitable drug level in the blood through a slow release rate. An interesting alternative to achieve a controlled release is the application of carrier materials such as polymers, cyclodextrins, and clays. Sodium montmorillonite (Na-MMT) is a biocompatible natural clay that allows the insertion of organic compounds in interlamellar space, owing to its high cation exchange capacity and large internal surface area. Bromopride (BPD) is an aminated compound with antiemetic properties classified as class II (low solubility, high permeability) of the Biopharmaceutical Classification System (BCS). Herein, the aim of the study was the development and investigation of a drug delivery system formed by intercalation of BPD with Na-MMT. The results indicate the successful intercalation of this API with the lamellar silicate, meanwhile, there was no evidence of BPD intercalation in organic montmorillonite. The Na-MMT/BPD molecular complex exhibits a sustained release in performed assays. Molecular dynamics simulations suggested that BPD molecules interact with the montmorillonite layer through ion-dipole interactions and also between BPD molecules, forming hydrogen bonds web into montmorillonite interlayer space. The new drug delivery system showed an alternative to achieve the BPD sustained release, which may improve its pharmacological performance in therapeutic applications.
Asunto(s)
Bentonita , Metoclopramida , Bentonita/química , Arcilla , Preparaciones de Acción Retardada , Metoclopramida/análogos & derivadosRESUMEN
A comprehensive forced degradation study for bromopride was carried out in accordance with International Conference on Harmonization (ICH) recommendations followed by the identification and prospecting of the major degradation products. The analytical quality by design (AQbD) concepts were used to develop a stability-indicating method for bromopride and five organic impurities quantitation by ultra-high performance liquid chromatography with UV detection (UHPLC-UV). Two screenings and one optimization design were performed, including a Monte Carlo simulation to assess the Method Operable Design Region (MODR). The AQbD approach provided a high degree of method understanding in a very short period of time, less than two weeks, and the validated MODR provided information on robust analytical conditions contributing to the assignment of suitable control strategies.
Asunto(s)
Cromatografía Líquida de Alta Presión , Límite de Detección , Metoclopramida/análogos & derivados , Método de Montecarlo , Reproducibilidad de los ResultadosRESUMEN
A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.
Asunto(s)
Carcinoma de Células Escamosas/complicaciones , Estreñimiento/etiología , Gastroparesia/etiología , Neoplasias Pulmonares/complicaciones , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Anciano , Antieméticos/uso terapéutico , Carcinoma de Células Escamosas/diagnóstico por imagen , Estreñimiento/diagnóstico , Estreñimiento/tratamiento farmacológico , Estreñimiento/fisiopatología , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/fisiopatología , Motilidad Gastrointestinal , Gastroparesia/diagnóstico , Gastroparesia/tratamiento farmacológico , Gastroparesia/fisiopatología , Glicerol/uso terapéutico , Humanos , Lactulosa/uso terapéutico , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Metoclopramida/análogos & derivados , Metoclopramida/uso terapéutico , Morfina/efectos adversos , Estreñimiento Inducido por Opioides/diagnóstico , Cuidados Paliativos , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/fisiopatología , Tramadol/efectos adversosRESUMEN
Bromopride is a prokinetic and antiemetic drug used to treat nausea and vomiting. Although its prescription is common in Brazil, there is a lack of studies about bromopride pharmacokinetics. Therefore, the aims of this study were to investigate the population pharmacokinetics of bromopride and to evaluate the influence of covariates on its absorption. This study is a retrospective analysis of data collected from bioequivalence studies. The data was modeled using MONOLIX 2018R2. Assuming one-compartment and linear elimination, the absorption phase was evaluated with different structural models. The model of sequential first- and zero-order with combined error and exponential inter-individual variability in all parameters best described the atypical absorption profile of bromopride. Population estimates were first-order absorption rate (ka) of 0.08 hâ¯-â¯1, fraction of dose absorbed by first-order (Fr) of 32.60%, duration of the zero-order absorption (Tk0) of 0.88â¯h with latency time (Tlag) of 0.47â¯h, volume of distribution of 230 l and clearance of 46.80 l hâ¯-â¯1. Bodyweight affects Tk0, dosage form was found to correlate with Tk0 and Tlag, while gender affects Tlag. However, simulations evaluating the clinical importance of these covariates on steady-state indicated minimal changes on bromopride exposure. The mixed absorption model was reasonable to describe the absorption process of bromopride because it had the flexibility to fit multiple-peaks profile and shows good agreement with physicochemical properties of drug.
Asunto(s)
Antieméticos/farmacocinética , Absorción Gastrointestinal/fisiología , Metoclopramida/análogos & derivados , Administración Oral , Adulto , Disponibilidad Biológica , Brasil , Femenino , Humanos , Cinética , Masculino , Metoclopramida/farmacocinética , Estudios RetrospectivosRESUMEN
Abstract Objective: To compare the effectiveness of a single intramuscular dose of bromopride, metoclopramide, or ondansetron for treating vomiting. Methods: Randomized controlled trial including children 1-12 years of age presenting with acute vomiting at the pediatric emergency department. Outcomes: Number of children that stopped vomiting at one, six, and 24 h following treatment; episodes of diarrhea; acceptance of oral liquids; intravenous rehydration; return to hospital and side effects. Results: There were 175 children who completed the study. Within the first hour after treatment, all drugs were equally effective, with ondansetron preventing vomiting in 100%, bromopride in 96.6%, and metoclopramide in 94.8% of children (p = 0.288). Within six hours, ondansetron was successful in preventing vomiting in 98.3% of children, compared to bromopride and metoclopramide, which were successful in 91.5% and 84.4% of patients, respectively (p = 0.023). Within 24 h, ondansetron was superior to both other agents, as it remained efficacious in reducing vomiting in 96.6% of children, as opposed to 67.8% and 67.2% with bromopride and metoclopramide, respectively (p = 0.001). The ondansetron group showed better acceptance of oral liquids (p = 0.05) when compared to the bromopride and metoclopramide. The ondansetron group did not show any side effects in 75.9% of cases, compared to 54.2% and 53.5% in the bromopride and metoclopramide groups, respectively. Somnolence was the most common side effect. Conclusions: A single dose of ondansetron is superior to bromopride and metoclopramide in preventing vomiting six hours and 24 h following treatment. Oral fluid intake after receiving medication was statistically better with Ondansetronwhile also having less side effects compared to the other two agents.
Resumo Objetivo: Para comparar a eficacia de uma unica dose intramuscular de bromoprida, metoclopramida ou ondansetrona no tratamento de vomito. Métodos: Ensaio controlado randomizado incluindo crianc¸as de 1 a 12 anos de idade que apresentam vomito agudo no departamento de emergencia pediatrica. Desfechos: Numero de crianças que pararam de vomitar 1, 6 e 24 horas apos o tratamento; episodios de diarreia; aceitac¸ao de liquidos orais; reidratac¸ao intravenosa, retorno ao hospital e efeitos colaterais. Resultados: 175 crianças concluiram o estudo. Na primeira hora apos o tratamento, todos os medicamentos foram igualmente eficazes, sendo que a ondansetrona preveniu vomito em 100%, a bromoprida em 96,6% e metoclopramida em 94,8% das crianças (p = 0,288). Em 6 horas, a ondansetrona mostrou sucesso na prevençao do vomito em 98,3% das crianças, em comparac¸ao a bromoprida e a metoclopramida, que mostraram sucesso em 91,5% e 84,4% dos pacientes, respectivamente (p = 0,023). Em 24 horas, a ondansetrona foi superior aos dois outros agentes, pois ela continuou eficaz na reduçao do vomito em 96,6% das crianças, diferente de 67,8% e 67,2% com bromoprida e metoclopramida, respectivamente (p = 0,001). O grupo de ondansetrona mostrou melhor aceitaçao de liquidos orais (p = 0,05) em comparaçao a bromoprida e metoclopramida. O grupo de ondansetrona nao mostrou efeitos colaterais em 75,9% dos casos, em comparaçao a 54,2% e 53,5% dos grupos de bromoprida e metoclopramida. O efeito colateral mais comum foi sonolencia. Conclusões: Uma unica dose de ondansetrona e superior a bromoprida e metoclopramida no tratamento de vomito 6 horas e 24 horas apos o tratamento. A ingestao de fluidos orais apos receber medicaçao foi estatisticamente melhor com ondansetrona, ao mesmo tempo em que tambem apresentando menos efeitos colaterais em comparaçao aos outros dois agentes.
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Vómitos/tratamiento farmacológico , Ondansetrón/administración & dosificación , Metoclopramida/administración & dosificación , Metoclopramida/análogos & derivados , Antieméticos/administración & dosificación , Enfermedad Aguda , Resultado del Tratamiento , Servicio de Urgencia en HospitalRESUMEN
OBJECTIVE: To compare the effectiveness of a single intramuscular dose of bromopride, metoclopramide, or ondansetron for treating vomiting. METHODS: Randomized controlled trial including children 1-12 years of age presenting with acute vomiting at the pediatric emergency department. OUTCOMES: Number of children that stopped vomiting at one, six, and 24h following treatment; episodes of diarrhea; acceptance of oral liquids; intravenous rehydration; return to hospital and side effects. RESULTS: There were 175 children who completed the study. Within the first hour after treatment, all drugs were equally effective, with ondansetron preventing vomiting in 100%, bromopride in 96.6%, and metoclopramide in 94.8% of children (p=0.288). Within six hours, ondansetron was successful in preventing vomiting in 98.3% of children, compared to bromopride and metoclopramide, which were successful in 91.5% and 84.4% of patients, respectively (p=0.023). Within 24h, ondansetron was superior to both other agents, as it remained efficacious in reducing vomiting in 96.6% of children, as opposed to 67.8% and 67.2% with bromopride and metoclopramide, respectively (p=0.001). The ondansetron group showed better acceptance of oral liquids (p=0.05) when compared to the bromopride and metoclopramide. The ondansetron group did not show any side effects in 75.9% of cases, compared to 54.2% and 53.5% in the bromopride and metoclopramide groups, respectively. Somnolence was the most common side effect. CONCLUSIONS: A single dose of ondansetron is superior to bromopride and metoclopramide in preventing vomiting six hours and 24h following treatment. Oral fluid intake after receiving medication was statistically better with Ondansetronwhile also having less side effects compared to the other two agents.
Asunto(s)
Antieméticos/administración & dosificación , Metoclopramida/análogos & derivados , Metoclopramida/administración & dosificación , Ondansetrón/administración & dosificación , Vómitos/tratamiento farmacológico , Enfermedad Aguda , Niño , Preescolar , Servicio de Urgencia en Hospital , Femenino , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.
Asunto(s)
Animales , Masculino , Antieméticos/farmacología , Colon Descendente/cirugía , Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Metoclopramida/análogos & derivados , Anastomosis Quirúrgica , Ciego/cirugía , Interferón gamma/análisis , Interleucina-1beta/análisis , /análisis , /análisis , Interleucinas/genética , Ligadura , Metaloproteinasa 1 de la Matriz/análisis , /análisis , /análisis , Metaloproteinasas de la Matriz/genética , Metoclopramida/farmacología , Punciones , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sepsis/etiología , Factor de Necrosis Tumoral alfa/análisis , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-ß, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.
Asunto(s)
Antieméticos/farmacología , Colon Descendente/cirugía , Expresión Génica/efectos de los fármacos , Interleucinas/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Metoclopramida/análogos & derivados , Anastomosis Quirúrgica , Animales , Ciego/cirugía , Interferón gamma/análisis , Interleucina-10/análisis , Interleucina-1beta/análisis , Interleucina-6/análisis , Interleucinas/genética , Ligadura , Masculino , Metaloproteinasa 1 de la Matriz/análisis , Metaloproteinasa 13 de la Matriz/análisis , Metaloproteinasa 8 de la Matriz/análisis , Metaloproteinasas de la Matriz/genética , Metoclopramida/farmacología , Punciones , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sepsis/etiología , Factor de Necrosis Tumoral alfa/análisis , Cicatrización de Heridas/efectos de los fármacosRESUMEN
A flow injection spectrophotometric procedure employing merging zones is proposed for direct bromopride determination in pharmaceutical formulations and biological fluids. The proposed method is based on the reaction between bromopride and p-dimethylaminocinnamaldehyde (p-DAC) in acid medium, in the presence of sodium dodecyl sulfate (SDS), resulting in formation of a violet product (λmax=565nm). Experimental design methodologies were used to optimize the experimental conditions. The Beer-Lambert law was obeyed in a bromopride concentration range of 3.63×10(-7) to 2.90×10(-5)molL(-1), with a correlation coefficient (r) of 0.9999. The limits of detection and quantification were 1.07×10(-7) and 3.57×10(-7)molL(-1), respectively. The proposed method was successfully applied to the determination of bromopride in pharmaceuticals and human urine, and recoveries of the drug from these media were in the ranges 99.6-101.2% and 98.6-102.1%, respectively. This new flow injection procedure does not require any sample pretreatment steps.
Asunto(s)
Antagonistas de Dopamina/orina , Análisis de Inyección de Flujo/instrumentación , Metoclopramida/análogos & derivados , Espectrofotometría/instrumentación , Cinamatos/química , Antagonistas de Dopamina/análisis , Monitoreo de Drogas/instrumentación , Diseño de Equipo , Humanos , Límite de Detección , Metoclopramida/análisis , Metoclopramida/orina , Preparaciones Farmacéuticas/químicaRESUMEN
PURPOSE: To assess the effect of prokinetic agents on abdominal wall wound healing in rats submitted to segmental colectomy and colonic anastomosis. METHODS: Sixty rats were randomly allocated into three groups according to the agents they would receive in the postoperative period: M (metoclopramide); B (bromopride); and C (control, saline 0.9%). Surgical procedures were performed identically in all animals, and consisted of a midline laparotomy followed by resection of a 1-cm segment of large bowel with end-to-end anastomosis. The abdominal wall was closed in two layers with running stitches. Abdominal wall samples were collected on the 3rd or 7th postoperative day for measurement of breaking (tensile) strength and histopathological assessment. RESULTS: There were no statistically significant differences in tensile strength of the abdominal wall scar between groups M, B, and C, nor between the three and seven days after surgery subgroups. On histopathological assessment, there were no statistically significant between-group differences in collagen deposition or number of fibroblasts at the wound site CONCLUSION: Use of the prokinetic drugs metoclopramide or bromopride had no effect on abdominal wall healing in rats submitted to segmental colectomy and colonic anastomosis.
Asunto(s)
Pared Abdominal , Colectomía , Colon/cirugía , Fármacos Gastrointestinales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Pared Abdominal/cirugía , Anastomosis Quirúrgica , Animales , Cicatriz/fisiopatología , Antagonistas de Dopamina/farmacología , Fármacos Gastrointestinales/uso terapéutico , Masculino , Metoclopramida/análogos & derivados , Metoclopramida/farmacología , Distribución Aleatoria , Ratas , Ratas Wistar , Resistencia a la Tracción , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To assess the effect of prokinetic agents on abdominal wall wound healing in rats submitted to segmental colectomy and colonic anastomosis. METHODS: Sixty rats were randomly allocated into three groups according to the agents they would receive in the postoperative period: M (metoclopramide); B (bromopride); and C (control, saline 0.9%). Surgical procedures were performed identically in all animals, and consisted of a midline laparotomy followed by resection of a 1-cm segment of large bowel with end-to-end anastomosis. The abdominal wall was closed in two layers with running stitches. Abdominal wall samples were collected on the 3rd or 7th postoperative day for measurement of breaking (tensile) strength and histopathological assessment. RESULTS: There were no statistically significant differences in tensile strength of the abdominal wall scar between groups M, B, and C, nor between the three and seven days after surgery subgroups. On histopathological assessment, there were no statistically significant between-group differences in collagen deposition or number of fibroblasts at the wound site CONCLUSION: Use of the prokinetic drugs metoclopramide or bromopride had no effect on abdominal wall healing in rats submitted to segmental colectomy and colonic anastomosis.
OBJETIVO: Avaliar os efeitos do uso de drogas prócinéticas na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo. MÉTODOS: Foram utilizados 60 ratos, alocados aleatoriamente em três grupos para receberem as seguintes medicações no período pós-operatório: M (metoclopramida); B (bromoprida) e C (solução salina a 0,9%). Os procedimentos cirúrgicos foram idênticos em todos os animais. Foi realizada laparotomia mediana, seguida de colectomia segmentar de 1-cm e anastomose colônica. O fechamento da parede abdominal foi feito em dois planos de sutura contínua. No 3° ou no 7° dia pós-operatório foram coletadas amostras da parede abdominal para medida da força de ruptura e avaliação histopatológica. RESULTADOS: Não houve diferença significativa entre os grupos no que diz respeito à força de ruptura da parede abdominal, nem entre os subgrupos no 3º e 7º dia após a cirurgia. À análise histopatológica não houve alterações na deposição de colágeno ou na quantidade de fibroblastos no sítio da cicatriz. CONCLUSÃO: O uso de drogas prócinéticas, metoclopramida ou de bromoprida, não interferiu na cicatrização da parede abdominal de ratos submetidos à colectomia segmentar e anastomose no cólon esquerdo.
Asunto(s)
Animales , Masculino , Ratas , Pared Abdominal , Colectomía , Colon/cirugía , Fármacos Gastrointestinales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Pared Abdominal/cirugía , Cicatriz/fisiopatología , Antagonistas de Dopamina/farmacología , Fármacos Gastrointestinales/uso terapéutico , Metoclopramida/análogos & derivados , Metoclopramida/farmacología , Distribución Aleatoria , Ratas Wistar , Resistencia a la Tracción , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. METHODS: Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. RESULTS: On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. CONCLUSION: In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery.
Asunto(s)
Antieméticos/farmacología , Colon/cirugía , Metoclopramida/análogos & derivados , Sepsis/fisiopatología , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Colágeno/análisis , Colon/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hidroxiprolina/análisis , Ligadura , Masculino , Metoclopramida/farmacología , Periodo Posoperatorio , Punciones , Ratas , Ratas Wistar , Sepsis/etiología , Resistencia a la TracciónRESUMEN
PURPOSE: To evaluate the effects of bromopride on the healing of left colonic anastomoses in rats with induced abdominal sepsis. METHODS: Forty rats were divided into two groups to receive either bromopride (experimental group- E) or saline (control group- C). Each group was divided into subgroups of ten animals each to be euthanized on third (E3 and C3) or seventh day (E7 and C7) after surgery. Sepsis was induced by cecal ligation and puncture. The rats underwent segmental left colon resection and end-to-end anastomosis. Adhesion formation, tensile strength and hydroxyproline concentration were assessed. Histomorphometry of collagen and histopathological analysis were also performed. RESULTS: On postoperative third day, anastomoses in bromopride-treated animals showed lower tensile strength (p=0.02) and greater reduction in hydroxyproline concentration (p=0.04) than in control animals. There was no statistical difference in these parameters on seventh day, and the remaining parameters were similar across subgroups. Collagen content was also similar across subgroups. CONCLUSION: In the presence of abdominal sepsis, the administration of bromopride was associated with decreased tensile strength and hydroxyproline concentration in left colonic anastomoses in rats three days after surgery.
OBJETIVO: Avaliar os efeitos da bromoprida sobre a cicatrização de anastomoses de cólon esquerdo de ratos na presença de sepse abdominal. MÉTODOS: Quarenta ratos distribuídos em grupos contendo 20 animais para administração de bromoprida ou salina. Cada grupo foi dividido em subgrupos contendo dez animais, para eutanásia no terceiro ou no sétimo dia de pós-operatório. A indução da sepse foi realizada pelo método de ligadura e punção do ceco. Foi realizada ressecção de um segmento do cólon esquerdo e anastomose término-terminal. À re-laparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, força de ruptura, concentração de hidroxiprolina e histomorfometria do colágeno. RESULTADOS: No 3° DPO, as anastomoses dos animais tratados com bromoprida apresentaram menor força de ruptura (p=0,02) e maior redução da concentração de hidroxiprolina (p=0,04) que os animais controle. Não houve diferença estatística quanto a estes parâmetros no 7° DPO. O conteúdo de colágeno foi semelhante entre os subgrupos. CONCLUSÃO: Na presença de sepse abdominal, o uso da bromoprida esteve associado à diminuição da força de ruptura e da concentração de hidroxiprolina das anastomoses do cólon esquerdo de ratos no 3° DPO.
Asunto(s)
Animales , Masculino , Ratas , Antieméticos/farmacología , Colon/cirugía , Metoclopramida/análogos & derivados , Sepsis/fisiopatología , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Colágeno/análisis , Colon/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hidroxiprolina/análisis , Ligadura , Metoclopramida/farmacología , Periodo Posoperatorio , Punciones , Ratas Wistar , Sepsis/etiología , Resistencia a la TracciónRESUMEN
OBJETIVO: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. MÉTODOS: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. RESULTADOS: Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. CONCLUSÃO: O uso da bromoprida está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.
OBJECTIVE: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. METHODS: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group-C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. RESULTS: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. CONCLUSION: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day.
Asunto(s)
Animales , Masculino , Ratas , Colon/efectos de los fármacos , Colon/cirugía , Enfermedades del Colon/prevención & control , Metoclopramida/análogos & derivados , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Metoclopramida/farmacología , Metoclopramida/uso terapéutico , Ratas Wistar , Adherencias Tisulares/prevención & controlRESUMEN
PURPOSE: Evaluate the effects of bromopride on abdominal wall healing of rats with induced peritoneal sepsis after segmental colectomy and colonic anastomosis. METHODS: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of bromopride (bromopride group - B) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (GB3 and GC3) or seventh postoperative day (GB7 and GC7). It was analyzed the following characteristics: breaking strength of the abdominal wall's wound; surgical and histopathological features of the abdominal wall; and clinical features of the rats. RESULTS: There was no difference between the groups in relation to the weight of the rats and the breaking strength of the abdominal wall's wound. The GB7 group presented less edema and less quantity of fibrin during histopathological evaluation compared to the GC7 group. CONCLUSION: Bromopride did not have harmful effects on the healing of abdominal wall in rats.
OBJETIVO: Avaliar o efeito da bromoprida, na cicatrização da ferida operatória da parede abdominal de ratos com sepse peritoneal experimentalmente induzida e submetidos a ressecção segmentar e anastomose de cólon esquerdo. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para administração de bromoprida (grupo bromoprida- B) ou solução de NaCl 0,9 por cento (grupo controle - C). Cada grupo foi dividido em subgrupos contendo 10 animais, para eutanásia no terceiro (GB3 e GC3) ou sétimo dia (GB7 e GE7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da eutanásia foram avaliadas as características cirúrgicas da cavidade abdominal e clínicas dos ratos. Foram coletados segmentos da parede para a avaliação histopatológica e de resistência tênsil da ferida operatória. RESULTADOS: Não houve diferenças entre os pesos dos ratos e resistência tênsil da ferida operatória nos dois grupos. Em relação a análise histopatológica, o grupo GB7 apresentou menos edema e menos fibrina que o grupo GC7. Não houve outras diferenças. CONCLUSÃO: A utilização de bromoprida não resultou em distúrbios ou retardo da cicatrização no grupo de ratos submetidos à laparotomia e anastomose término-terminal em condições de sepse peritoneal.
Asunto(s)
Animales , Masculino , Ratas , Pared Abdominal/cirugía , Antieméticos/farmacología , Metoclopramida/análogos & derivados , Peritonitis/complicaciones , Sepsis/complicaciones , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica/métodos , Colectomía , Metoclopramida/farmacología , Peritonitis/fisiopatología , Ratas Wistar , Sepsis/fisiopatologíaRESUMEN
PURPOSE: Evaluate the effects of bromopride on abdominal wall healing of rats with induced peritoneal sepsis after segmental colectomy and colonic anastomosis. METHODS: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of bromopride (bromopride group - B) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (GB3 and GC3) or seventh postoperative day (GB7 and GC7). It was analyzed the following characteristics: breaking strength of the abdominal wall's wound; surgical and histopathological features of the abdominal wall; and clinical features of the rats. RESULTS: There was no difference between the groups in relation to the weight of the rats and the breaking strength of the abdominal wall's wound. The GB7 group presented less edema and less quantity of fibrin during histopathological evaluation compared to the GC7 group. CONCLUSION: Bromopride did not have harmful effects on the healing of abdominal wall in rats.
Asunto(s)
Pared Abdominal/cirugía , Antieméticos/farmacología , Metoclopramida/análogos & derivados , Peritonitis/complicaciones , Sepsis/complicaciones , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica/métodos , Animales , Colectomía , Masculino , Metoclopramida/farmacología , Peritonitis/fisiopatología , Ratas , Ratas Wistar , Sepsis/fisiopatologíaRESUMEN
OBJECTIVE: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. METHODS: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group-C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. RESULTS: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. CONCLUSION: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day.
Asunto(s)
Colon/efectos de los fármacos , Colon/cirugía , Enfermedades del Colon/prevención & control , Metoclopramida/análogos & derivados , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Masculino , Metoclopramida/farmacología , Metoclopramida/uso terapéutico , Ratas , Ratas Wistar , Adherencias Tisulares/prevención & controlRESUMEN
OBJECTIVE: To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI). DESIGN AND SETTING: Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006. PATIENTS: Twenty-five patients with BCC-BSI. DESIGN: After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar chi(2) adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using SpeI. RESULTS: The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals. CONCLUSION: Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.
Asunto(s)
Bacteriemia , Complejo Burkholderia cepacia , Brotes de Enfermedades , Contaminación de Equipos , Inyecciones Intravenosas/efectos adversos , Metoclopramida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/epidemiología , Bacteriemia/microbiología , Brasil/epidemiología , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/microbiología , Complejo Burkholderia cepacia/clasificación , Complejo Burkholderia cepacia/genética , Complejo Burkholderia cepacia/aislamiento & purificación , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Estudios Cruzados , Electroforesis en Gel de Campo Pulsado , Femenino , Hospitales Privados/estadística & datos numéricos , Hospitales Públicos/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Humanos , Masculino , Metoclopramida/administración & dosificación , Persona de Mediana EdadRESUMEN
PURPOSES: To determine the efficacy of bromopride in the prophylaxis of nausea during fluorescein angiography, when compared with a placebo. METHODS: The study was a double-masked random clinical trial, between December of 2004 and April of 2005. Examinations were performed with 20% intravenous fluorescein sodium in a single dose of 2.5 ml. The patients were divided into two groups: group 1, patients who received a 2 ml intravenous dose of 5 mg/ml bromopride and group 2, patients who received a 2 ml intravenous dose of 0.9% sodium chloride (placebo), both 20 minutes before the dye injection. Cases of nausea were observed during and after the examination. RESULTS: 352 patients were enrolled, 176 in each group. Cases of nausea were observed in 12 (6.8%) patients of the bromopride group and in 11 (6.3%) patients of the placebo group (p<0.829 - relative risk=1.05). CONCLUSION: Bromopride did not prevent the occurrence of nausea in fluorescein angiography, when compared with a placebo.
Asunto(s)
Antieméticos/uso terapéutico , Angiografía con Fluoresceína/efectos adversos , Metoclopramida/análogos & derivados , Náusea/prevención & control , Método Doble Ciego , Femenino , Humanos , Masculino , Metoclopramida/uso terapéutico , Persona de Mediana Edad , Náusea/etiología , Resultado del TratamientoRESUMEN
A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method for the quantification of bromopride I in human plasma is presented. Sample preparation consisted of the addition of procainamide II as the internal standard, liquid-liquid extraction in alkaline conditions using hexane-ethyl acetate (1 : 1, v/v) as the extracting solvent, followed by centrifugation, evaporation of the solvent and sample reconstitution in acetonitrile. Both I and II (internal standard, IS) were analyzed using a C18 column and the mobile-phase acetonitrile-water (formic acid 0.1%). The eluted compounds were monitored using electrospray tandem mass spectrometry. The analyses were carried out by multiple reaction monitoring (MRM) using the parent-to-daughter combinations of m/z 344.20 > 271.00 and m/z 236.30 > 163.10. The areas of peaks from analyte and IS were used for quantification of I. The achieved limit of quantification was 1.0 ng/ml and the assay exhibited a linear dynamic range of 1-100.0 ng/ml and gave a correlation coefficient (r) of 0.995 or better. Validation results on linearity, specificity, accuracy, precision and stability, as well as application to the analysis of samples taken up to 24 h after oral administration of 10 mg of I in healthy volunteers demonstrated the applicability to bioequivalence studies.