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Interaction of insulin with prokinetic drugs in STZ-induced diabetic mice

World Journal of Gastrointestinal Pharmacology and Therapeutics 2013年第2期4卷 28-38页

作者： Mohamed A Fouad Shalaby Hekma A Abd El Latif Mostafa E El Sayed Department of Pharmacology Kahira Pharmaceutical CompanyCairo 793Egypt Faculty of Pharmacy Cairo UniversityCairo 11562Egypt

AIM:To study the possible interactions of metoclopramide,domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various ***:Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels,small intestinal transit(SIT),gastric emptying(GE),xylose absorption and glucose tolerance *** were given insulin 2 IU/kg s.c.,metoclopramide 20 mg/kg p.o.,domperidone 20 mg/kg *** erythromycin 6 mg/kg *** and in *** were also normal and diabetic control *** first set of experiments was carried out to investigate the subchronic effect on blood glucose and serum insulin levels in diabetic mice of one week of daily dose administration of the tested drugs individually as well as the combination of insulin with each prokinetic *** other five sets of experiments were carried out to investigate the acute effect of a single dose of each drug individually and in combination on blood glucose and serum insulin levels,SIT,GE,oral xylose absorption and glucose tolerance ***:The study included the prokinetic drugs metoclopramide(20 mg/kg),domperidone(20 mg/kg) and erythromycin(6 mg/kg),as well as insulin(2 IU/kg),which was individually effective in decreasing SIT,enhancing GE and increasing xylose absorption significantly in diabetic *** tended to decrease blood glucose level and increase serum insulin level after 1 wk of daily administration in diabetic *** potentiated the effect of insulin on blood glucose level and serum insulin level whereas other prokinetic agents failed to do so after repeated dose administration in diabetic *** or erythromycin in combination with insulin significantly decreased SIT,in diabetic mice,to lower levels than with insulin *** of prokinetic drugs along with insulin antagonized the action of insulin on xylose abs

关键词： Streptozotocin Gastrointestinal motility Insulin prokinetic drugs Intestinal absorption

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Effect of DA-9701 on gastric emptying in a mouse model: Assessment by ^(13)C-octanoic acid breath test

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World Journal of Gastroenterology 2013年第27期19卷 4380-4385页

作者： Chul-Hyun Lim Myung-Gyu Choi Hyeyeon Park Myong Ki Baeg Jae Myung Park Department of Internal Medicine The Catholic University of Korea College of Medicine

AIM:To evaluate the effects of DA-9701 on the gastric emptying of a solid meal using the 13C-octanoic acid breath test in a mouse model. METHODS:Male C57BL/6 mice aged > 8 wk and with body weights of 20-25 g were used in this study. The solid test meal consisted of 200 mg of egg yolk labeled with 1.5 L/g 13C-octanoic acid. The mice were placed in a 130 mL chamber flushed with air at a flow speed of 200 mL/min. Breath samples were collected for 6 h. The half-emptying time and lag phase were calculated using a modified power exponential model. To assess the reproducibility of the 13C-octanoic acid breath test, the breath test was performed two times at intervals of one week in ten mice without drug treatment. To assess the gastrokinetic effects of DA-9701, the breath test was performed three times in another twelve mice, with a randomized crossover sequence of three drug treatments:DA-9701 3 mg/kg, erythromycin 6 mg/kg, or saline. Each breath test was performed at an interval of one week. RESULTS:Repeatedly measured half gastric emptying time of ten mice without drug treatment showed 0.856 of the intraclass correlation coefficient for the half gastric emptying time (P = 0.004). The mean cumulative excretion curve for the 13C-octanoic acid breath test showed accelerated gastric emptying after DA-9701 treatment compared with the saline control (P = 0.028). The median half gastric emptying time after the DA-9701 treatment was significantly shorter than after the saline treatment [122.4 min (109.0-137.9 min) vs 134.5 min (128.4-167.0 min), respectively; P = 0.028] and similar to that after the erythromycin treatment [123.3 min (112.9-138.2 min)]. The lag phase, which was defined as the period taken to empty 15% of a meal, was significantly shorter after the DA-9701 treatment than after the saline treatment [48.1 min (44.6-57.1 min) vs 52.6 min (49.45-57.4 min), respectively; P = 0.049]. CONCLUSION:The novel prokinetic agent DA-9701 accelerated gastric emptying, assessed w

关键词： DA-9701 Gastric emptying prokinetic agent Breath test Functional dyspepsia

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Gastroparesis: Current diagnostic challenges and management considerations

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World Journal of Gastroenterology 2009年第1期15卷 25-37页

作者： Shamaila Waseem Baharak Moshiree Peter V Draganov Department of Pediatric Gastroenterology Hepatology and Nutrition University of FloridaGainesville Florida 32610 United States Department of Gastroenterology Hepatology and Nutrition University of FloridaGainesville Florida 32610 United States

Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.

关键词： Gastroparesis, Nausea Vomiting prokinetic Therapy

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Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

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World Journal of Gastroenterology 2007年第11期13卷 1706-1710页

作者： Bhavneesh Sharma Manisha Sharma Mradul Kumar Daga Gopal Krishan Sachdev Elliott Bondi Brookdale University Hospital and Medical Center Division of Pulmonary and Critical Care Medicine State University of New York Brooklyn New York 11212 United States University of Delhi Maulana Azad Medical College Divisions of Pulmonary Medicine and Gastroenterology New Delhi 110002 India

AIM： To study the effect of combined omeprazole（Ome） and domperidone（Dom） therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS： We selected 198 asthmatics with gastro- esophageal reflux diagnosed by 24-h esophageal pH moni- toring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk （1：1 double-blind randomization）. Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were： mean daily daytime and nighttime asthma symptom scores. Mean daily reflux symptom scores, albuterol use as rescue medication （number of puffs）, daytime and nighttime peak expiratory flow rate （PEFR）, postbronchodilator forced expiratory volume in 1 second （FEVl） and postbronchodilator forced vital capacity （FVC） were secondary outcome measures. RESULTS： Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score （17.4% vs 8.9 %）, nighttime asthma symptom score （19.6% vs 5.4%）, reflux symptom score （8.7% vs 1.6%） and rescue medication use （23.2% vs 3.1%） after antireflux therapy compared to mean change in placebo group （P 〈 0.001）. There was significant improvement in morning PEFR （7.9% vs 0.2%）, evening PEFR （9.8% vs 0.5%）, FEW （11.1% vs 3.78%） and FVC （9.3%vs 1.52%） in the antireflux therapy group compared to placebo on comparng the mean change from baseline after 16 wk （P 〈 0.01） CONCLUSION： Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal reflux may be beneficial by reducing asthma symptoms, rescuing medi- cation use, and improving pulmonary function.

关键词： Asthma Reflux Gastroesophageal reflux disease Antireflux therapy prokinetic Omeprazole

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Effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy

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World Journal of Gastroenterology 2005年第31期11卷 4865-4868页

作者： Wai K Leung Francis KL Chan Sara SL Fung Mei-Yin Wong Joseph JY Sung Digestive Diseases Center

AIM： To determine the effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy. METHODS： Consecutive patients who underwent capsule endoscopy during the 16-mo study period were either given 250 mg oral erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The gastric and small bowel transit time, and the small bowel image quality were compared. RESULTS： Twenty-four patients received oral erythromycin whereas 14 patients were not given any prokinetic agent. Patients who received erythromycin had a significantly lower gastric transit time than control （16 min vs70 min, P= 0.005）, whereas the small bowel transit time was comparable between the two groups （227 rain vs 183 min, P= 0.18）. Incomplete small bowel examination was found in three patients of the control group and in one patient of the erythromycin group. There was no significant difference in the overall quality of small bowel images between the two groups. A marked reduction in gastric transit time was noted in two patients who had repeat capsule endoscopy after oral erythromycin. CONCLUSION： Use of oral erythromycin significantly reduces the gastric transit time of capsule endoscopy.

关键词： Capsule endoscopy Erythromycin prokinetic

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Pharmacological therapy of feed intolerance in the critically ills

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2014年第3期5卷 148-155页

作者： Nam Q Nguyen Departments of Gastroenterology and Hepatol-ogy Royal Adelaide Hospital5000 South AustraliaAustralia Discipline of Medicine University of Ad-elaideNorth TerraceAdelaide5000 South AustraliaAustralia

Feed intolerance in the setting of critical illness is associated with higher morbidity and mortality,and thusrequires promptly and effective treatment. prokineticagents are currently considered as the first-line therapygiven issues relating to parenteral nutrition and post-pyloric placement. Currently,the agents of choice areerythromycin and metoclopramide,either alone or incombination,which are highly effective with relativelylow incidence of cardiac,hemodynamic or neurologicaladverse effects. Diarrhea,however,can occur in up to 49% of patients who are treated with the dual prokinetic therapy,which is not associated with Clostridiumdifficile infection and settled soon after the cessation ofthe drugs. Hence,the use of prokinetic therapy over along period or for prophylactic purpose must be avoided,and the indication for ongoing use of the drug(s)must be reviewed frequently. Second line therapy,suchas total parenteral nutrition and post-pyloric feeding,must be considered once adverse effects relating theprokinetic therapy develop.

关键词： Adverse effects Critical illness Enteral feeding Feed intolerance prokinetic therapy

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Fixed Dose Combination of Magaldrate Plus Domperidone Is More Effective than Domperidone Alone in the Treatment of Patients with Gastroesophageal Reflux Symptoms: A Randomized Double-Blind Study

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Pharmacology & Pharmacy 2014年第2期5卷 216-223页

作者： Shendel Nyx Rodríguez-Sánchez Héctor Isaac Rocha-González Cecilia Fernández del Valle-Laisequilla Juan Rodríguez-Silverio Francisco Javier Flores-Murrieta Juan Gerardo Reyes-García Productos Medix S.A. de C.V. México City Mexico Sección de Estudios de Posgrado e Investigación Escuela Superior de Medicina del Instituto Politécnico Nacional Mexico City Mexico Sección de Estudios de Posgrado e Investigación Escuela Superior de Medicina del Instituto Politécnico Nacional Mexico City Mexico Instituto Nacional de Enfermedades Respiratorias Secretaría de Salud Mexico City Mexico

Gastroeophageal reflux is a condition in which the acidified liquid content of the stomach backs up into the esophagus. The antiacid magaldrate and prokinetic domperidone are two drugs clinically used for the treatment of gastroesophageal reflux symptoms. However, the evidence of a superior effectiveness of this combination in comparison with individual drugs is lacking. A double-blind, randomized and comparative clinical trial study was designed to characterize the efficacy and safety of a fixed dose combination of magaldrate (800 mg)/domperidone (10 mg) against domperidone alone (10 mg), in patients with gastroesophageal reflux symptoms. One hundred patients with gastroesophageal reflux diagnosed by Carlsson scale were randomized to receive a chewable tablet of a fixed dose of magaldrate/domperidone combination or domperidone alone four times each day during a month. Magaldrate/domperidone combination showed a superior efficacy to decrease global esophageal (pyrosis, regurgitation, dysphagia, hiccup, gastroparesis, sialorrhea, globus pharyngeus and nausea) and extraesophageal (chronic cough, hoarseness, asthmatiform syndrome, laryngitis, pharyngitis, halitosis and chest pain) reflux symptoms than domperidone alone. In addition, magaldrate/domperidone combination improved in a statistically manner the quality of life of patients with gastroesophageal reflux respect to monotherapy, and more patients perceived the combination as a better treatment. Both treatments were well tolerated. Data suggest that oral magaldrate/domperidone mixture could be a better option in the treatment of gastroesophageal reflux symptoms than only domperidone.

关键词： Antiacid Domperidone Gastroesophageal Reflux Magaldrate prokinetic

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Finding the solution for incomplete small bowel capsule endoscopy

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World Journal of Gastrointestinal Endoscopy 2013年第12期5卷 595-599页

作者： José Cotter Francisca Dias de Castro Joana Magalhes Maria Joo Moreira Bruno Rosa Gastroenterology Department Centro Hospitalar do Alto Ave Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho ICVS/3B’s PT Government Associate Laboratory

AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February *** location was systematically checked one hour after ingestion using *** it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 *** the capsule remained in the stomach a second dose of10 mg of domperidone was administered *** another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)*** rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical *** control group included 307 patients,with 48(15.6%)*** RTV group included 82 patients,with3(3.7%)IE,P=*** the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=*** did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.

关键词： Small bowel capsule endoscopy prokinetic drugs Domperidone Incomplete examination

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