Role and safety of prokinetic drugs in the treatment of upper gastrointestinal motility disorders: an Indian perspective

Upper gastrointestinal (GI) motility disorders such as functional dyspepsia (FD), gastroesophageal reflux disease, and gastroparesis are associated with symptoms such as acid reflux, regurgitation, bloating, and heartburn. This review summarizes the prevalence, diagnosis and management of upper GI motility disorders in clinical practice in India, with focus on the use of prokinetics. Lifestyle and dietary modifications, psychotherapy, and pharmacotherapy form the armamentarium for management of motility disorders. Among pharmacotherapies, prokinetics increase gastric emptying and provide symptomatic relief. However, neurological and cardiovascular safety issues are associated with commonly prescribed prokinetics making it important to judiciously select an appropriate drug after weighing out its risk-benefit profile. While metoclopramide, domperidone, and levosulpiride are widely prescribed prokinetics in Indian clinical practice, they are associated with adverse effects such as extrapyramidal symptoms (EPS) and cardiovascular side effects. Itopride, which is a prokinetic with dual mechanism of action, has been found to have equivalent efficacy to other prokinetics and has shown significant improvement in quality of life and symptoms in randomized controlled trials in patients with FD. It acts as a D2 receptor antagonist and acetylcholinesterase inhibitor. Both these actions cause increase in acetylcholine levels, which increases gastric motility. Itopride also has negligible cardiac and neurological safety concerns. Thus, it is a relatively safer molecule compared with other prokinetics, with no EPS or cardiotoxicity concerns and can be used for the long-term management of upper GI motility disorders in a wide pool of patient groups either alone or in combination with other drug classes.

The comparative effects of Itopride and Levosulpiride orally used in patients suffering from Non-ulcer dyspepsia

Background: Itopride and Levosulpiride both comes under the group of Prokinetic drugs. These drugs are used for the treatment of non-ulcer dyspepsia, heart burn, nausea and vomiting. Both drugs act on dopaminergic D2 receptor as antagonist and increases the concentration of acetylcholine so that gastric peristalsis will be increase and that time pressure at lower oesophageal sphincter will be increase thus gastric motility increases and there will be good gastro-duodenal co-ordination.Method: This study has to conduct on patients with complains of non-ulcer dyspepsia attended Medical outdoor and department of pharmacology of SKMCH Muzaffarpur, Bihar, India. The total 60 patients have to include in the study, which have to randomly divide in two groups. Group A (itopride) comprising of 30 patients and Group B (Levosulpiride) comprising of 30 patients. Patients have to randomly allocate to receive one tablet of itopride hydrochloride, 50 mg three times daily before meal and one tablet Levosulpiride of 75 mg three times daily before meal. Authors have to enroll the patients at the interval of two weeks and continue it upto 3 months.Results: Study did not found any remarkable change in biochemistry profile. Only QT prolongation changes were found in two patients, but no serious cardiac toxicity was observed with patient receiving Levosulpiride. Neither QT prolongation nor serious cardiac toxicity was observed with itopride hydrochloride therapy.Conclusions: In present study, efficacy of Itopride was comparable to Levosulpiride in relieving the symptoms of non-ulcer dyspepsia. Both the drugs were clinically and biochemically well tolerated. QT prolongation changes were found in two patients, but no serious cardiac toxicity was observed with patient receiving Levosulpiride. Itopride does not show cardiac toxicity and any changes in ECG.

Clinical Observation of Itopride Combined with Esomeprazole Magnesium in the Treatment of Esophageal Motility Dysfunction-induced Gastroesophageal Reflux Disease / 中国药房

OBJECTIVE:To investigate the clinical efficacy of itopride combined with esomeprazole magnesium in the treat-ment of esophageal motility dysfunction-induced gastroesophageal reflux disease(GERD). METHODS:A total of 100 patients with esophageal motility dysfunction-induced GERD were selected from our hospital during Sept. 2015-Sept. 2016,and then divided into control group and observation group according to random number table,with 50 cases in each group. Control group was given Esomeprazole magnesium enteric-coated tablets 40 mg,po,qd. Observation group was additionally given Itopride hydrochloride tablets 50 mg,po,tid,on the basis of control group. Both groups received treatment for consecutive 6 weeks. Clinical efficacies of 2 groups were observed,and symptom scores,LES resting pressure,liquid and solid swallowing and peristaltic pressure of esopha-geal body were observed before and after treatment. The occurrence of ADR was recorded. RESULTS:Total response rate of obser-vation group was 94.0％,which was significantly higher than 78.0％ of control group,with statistical significance(P<0.05). Be-fore treatment,there was no statistical significance in symptom scores,LES resting pressure,liquid and solid swallowing or peri-staltic pressure of esophageal body between 2 groups(P>0.05). After treatment,symptom scores of 2 groups were decreased sig-nificantly,and observation group was significantly lower than control group,with statistical significance (P<0.05). Compared with before treatment,LES resting pressure of observation group was increased significantly,and significantly higher than that of control group,with statistical significance (P<0.05). Success rate of liquid swallowing increased significantly in 2 groups,and that of observation group was significantly higher than that of control group,with statistical significance(P<0.05). Success rate of solid swallowing,liquid and solid peristaltic pressure of esophageal body(near segment,middle segment and far segment)in con-trol group were higher than before treatment,without statistical significance (P>0.05). Success rate of solid swallowing, liquid and solid peristaltic pressure of esophageal body(near segment,middle segment and far segment)in observation group were signifi-cantly higher than before treatment,and significantly higher than control group at corresponding period,with statistical significance (P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:For esophageal motility dysfunction-in-duced GERD,itopride combined with esomeprazole magnesium can significantly improve clinical symptom,effectively increase LES resting pressure,strengthen esophageal motor function,improve success rate of esophageal swallowing and enhance anti-gas-troesophageal reflux ability with good safety.

Development and Validation of a Stability Indicating HPLC Method for the Simultaneous Analysis of Esomeprazole and Itopride in Bulk and In Capsules.

A rapid, simple, selective, precise, and accurate stability indicating HPLC method has been developed and validated for the simultaneous analysis of esomeprazole and itopride in bulk and in capsule form. An isocratic separation was achieved using a Hypersil C4 (250 x 4.6 mm), 5 μm particle size column with a flow rate of 1 mL/min and photodiode array detector at 272 nm. The mobile phase consisted of 0.1M dipotassium hydrogen phosphate: acetonitrile (40:60 v/v). The method was validated for selectivity, specificity, linearity, precision, accuracy and robustness. The selectivity of the method was determined by assessing interference from the placebo, components of mobile phase and common excipients in pharmaceutical formulations. Whereas, specificity was established by stress degradation studies. The method was linear over the concentration range 40–120 μg/mL (R2 = 0.9999) and 150-450 μg/mL (R2 = 0.9999) for esomeprazole and itopride, respectively. Limit of detection is 0.207 and 0.724 μg/mL & Limit of quantitation is 0.691 and 2.415 μg/mL for esomeprazole and itopride, respectively. The precision and accuracy of the method was found to be acceptable. The method was found to be robust and suitable for the simultaneous analysis of esomeprazole and itopride in a capsule formulation. Degradation products resulting from the stress studies did not interfere with the detection and quantification of esomeprazole and itopride. The proposed HPLC method is thus stability-indicating.

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia

BACKGROUND/AIMS: Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. METHODS: Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. RESULTS: We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as > or = 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. CONCLUSIONS: DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety.

Comparative evaluation of itopride and domperidone in gastroesophageal reflux disease.

Background: Gastroesophageal reflux disease (GERD) presents in various ways in terms of symptoms and severity. This study was conducted to assess the severity of GERD patients and to evaluate the effect of itopride and domperidone on symptoms and severity of GERD. Methods: A single-blind study was carried out in 70 patients. Group A (n=35) patients were kept on itopride therapy, 50 mg thrice a day before meal. Group B (n=35) patients were kept on domperidone therapy, 10 mg thrice a day before meal. Patients of both groups were given rabeprazole, 20 mg once a day for hyperacidity. Patients served their own control. Each patient was followed-up at 2 weeks interval up to 8 weeks. Results: The most common symptom was heartburn, present in 95.71% patients. Regurgitation was the next most common symptom (65.71%). The most common lesion seen endoscopically (according to Savary Miller classification) was grade I (38.57%). In 24.29% patient, only symptoms of GERD were present without any endoscopically visible mucosal injury. At the end of 2, 4, 6, and 8 weeks, relief of symptoms was more with a combination of itopride and rabeprazole in comparison to the combination of domperidane and rabeprazole, but the difference was statistically insignificant. Healing rate at the end of 4th and 8th week was slight better with a combination of itopride and rabeprazole, but the difference again was statistically insignificant. Conclusion: Combination of itopride and rabeprazole showed insignificantly better results, both symptomatically and endoscopically in comparison to the combination of domperidone and rabeprazole.

Applying Novel Nutrient Drink to Clinical Trial of Functional Dyspepsia

BACKGROUND/AIMS: The drink test has been regarded as a surrogate marker of gastric accommodation. The aims of this study were to develop a novel nutrient drink test (NDT) protocol and investigate its potential for application to a clinical trial of functional dyspepsia (FD). METHODS: A novel NDT was designed, involving drinking 125 mL of nutrient 4 times at 5-minute intervals or until maximal tolerability. Healthy volunteers and patients with FD rated their symptoms every 5 minutes for 20 minutes in a developmental study. Patients with FD were enrolled in an open trial of itopride for 4 weeks. NDT was performed before and after treatment. Improvement of integrative symptoms score during NDT after treatment for more than 50% compared with baseline was defined as responder. RESULTS: Total aggregate symptom scores, sum of symptom scores measured during NDT, were higher in FD patients (n = 40, 368.1 +/- 245.3) than in controls (n = 19, 215.9 +/- 171.2) (P = 0.018) in a developmental study. In an open trial of itopride, symptom scores measured during NDT decreased significantly at all time points after treatment in responders (n = 49), whereas did not in non-responders (n = 25). Total aggregate symptom score for NDT correlated significantly with integrative dyspeptic symptom score, sum of 8 symptom scores of NDI questionnaire, at baseline (r = 0.374, P = 0.001) and after treatment (r = 0.480, P < 0.001). CONCLUSIONS: Our novel NDT can quantify dyspeptic symptoms and reflected therapeutic effects of itopride treatment in a clinical trial of FD patients. This NDT can be used as an effective parameter in clinical trials or drug development programs for assessing effects of novel therapies on postprandial symptoms.

Clinical observation of itopride and esomeprazole combining with deanxit in treating functional dyspepsia / 中国基层医药

Objective To investigate the clinical effect of Itopride and esomeprazole combining with deanxit in treating functional dyspepsia ( FD) .Methods Sixty-two patients meeting Rome Ⅲcriterion were randomly divided into the therapy groups which were treated with Itopride and esomeprazole combining with deanxit and the control groups which were treated with Itopride and esomeprazole for 4 weeks respectively .Symptom scoring was done before and after the treatment .Results The symptoms were remarkably improved , there was significant difference in the therapeutic effect between the two groups (P<0.05).The total efficiency was more obvious in the therapy group . Conclusion Itopride and esomeprazole combining with deanxit can produce an effect on the treatment of FD .Itopride and esomeprazole combining with deanxit has better clinical effect than Itopride and esomeprazole on the treatment of FD.

Investigation on the efficacy and safety of omeprazole combined itopride in the treatment of functional dyspepsia / 中国基层医药

Objective To study the effect of omeprazole combined itopride in treatment of functional dyspepsia and the safety.Methods 246 patients with functional dyspepsia were randomly divided into three groups,each group of 82 cases.Group A was treated with omeprazole,20mg each time,twice every day.Group B was treated with itopride,50mg each time,three times every day.Group C was treated with omeprazole combined itopride.All groups were treated for four weeks.Improvement of symptoms,clinical curative effect and safety were observed.Results The effective rate of early enough and after dinner full bilge symptoms of group C were 95.1％ and 95.3％,which were significantly higher than 64.6％ and 63.6％ of group A.The effective rate of abdominal pain and epigastric voiding symptoms of group C were 93.1％ and 90.8％,which were significantly higher than 67.2％ and 65.1％ of group B.The total effective rate of group C was 91.5％,which was significantly higher than 69.5％ of group A and 73.2％ of group B.All differences were statistically significant (P ＜ 0.05).Conclusion Omeprazole combined itopride in treatment of functional dyspepsia has definite curative effect,which is safety and worth of clinical promotion and popularization.

Effects of itopride prior to capsule endoscopy / 中华消化内镜杂志

ObjectiveTo evaluate the clinical effects of oral administration of itopride prior to capsule endoscopy on bowel preparation.MethodsA total of 40 patients who underwent capsule endoseopy from April,2010 to April,2011 were randomly assigned to the medication group and the control group (n =20 per group).The medication group took itopride on the day before capsule endoscopy.The two groups underwent the same procedure for bowel preparation.Clearance,gastric transit and intestinal transit of capsule endoscope,lesion detection rates were compared between the two groups.Results Bowel preparation of high quality in the medication group was 80％ (16/20),significantly higher than that (45％,9/20) in the control group (P ＜ 0.05 ).The mean gastric and intestinal transit times in the medication group were 31 min and 251 min,respectively,significantly shorter than those in the control group (P ＜ 0.05).While lesion detection rate in the medication group (60％,12/20) was significantly higher than that of the control (40％,8/20) (P ＜ 0.05).ConclusionOral itopride is of better clinical value for capsule endoscopy preparation.

The effect analysis of omeprazole or famotidine combined with itopride in the treatment of reflux esophagitis / 中国基层医药

Objective To observe the effect of omeprazole or famotidine combined with itopride in the treatment of reflux esophagitis.Methods 86 patients with reflux esophagitis were randomly divided into two groups,which group A with 43 eases was treated with omeprazole combined with itopride,and group B with 43 cases was treated with famotidine combined with itopride.The clinical effect and main symptoms were observed and compared.Results The total effective rate in group A was 91.3％,significantly higher than that of group B ( 71.4％ ) ( x2 =5.460,P ＜0.05 ).After treatment,the scores of heartburn,acid reflux and chest pain were significantly decreased ( all P ＜ 0.05 )in both two groups.Moreover,the scores of heartburn,acid reflux and chest pain in group A after treatment were significantly lower than those of group B ( all P ＜ 0.05 ).Conclusion Omeprazole combined with itopride in the treatment of reflux esophagitis is better than famotidine combined with itopride.

Meta-analysis of itopride therapy in functional dyspepsia / 中华消化杂志

Objective To evaluate the efficacy and safety of itopride in the treatment of functional dyspepsia (FD) according to the data of published clinical studies.Methods The papers about randomized controlled trials (RCT) of itopride in treatment of FD were searched from Cochrane library,EMBASE,PubMed,Elsevier,web of science (ISI),China national knonledge internet (CNKI),VIP Chinese Scientific and Technologic Periodical Database and Wanfang data,and the feature information in the studies were extracted.The relative risk (RR) value was used for count data and the weighted mean difference (WMD) was used for measurement data.The proper effect model was selected according to the results of heterogeneity test and the publication bias was investigated through visual inspection of funnel plots.Results A total of nine RCT met the inclusion standard.Of 2620 FD cases,1372 received itopride treatment and 1248 cases received placebo or other medicine as control treatment.The RR value of total effective rates,postprandial fullness and early satiety effective rates in itopride treated FD patients was 1.11 (95％CI:1.01,1.21; P=0.02),1.18 (95％CI:1.04,1.33; P=0.009),1.24 (95％CI:1.01,1.53; P=0.04),which showed the curative effects of itropride group were all better than those of control group.However there was no statistical significance in epigastric discomfort.The WMD of effective rates evaluated with the leeds dyspepsia questionnaire (LDQ) score was-1.38 (95％CI:-1.75,-1.01; P＜0.01),which showed the curative effect of itropride group was better than that of control group.For safety,the adverse effects rates of itopride groups were similar with control groups.The funnel plots of each inspection index presented wide bottom,narrow up and symmetrical graphics,which indicated that there was no publication bias.Conclusion Itopride has better efficacy in general symptoms,postprandial fullness,early satiety and LDQ score in FD patients,and few effects are detected.

Stability indicating high performance thin-layer chromatographic method for simultaneous estimation of pantoprazole sodium and itopride hydrochloride in combined dosage form / 药物分析学报

A specific, precise and stability indicating high-performance thin-layer chromatographic method for simultaneous estimation of pantoprazole sodium and itopride hydrochloride in pharmaceutical formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F254 as the stationary phase. The solvent system consisted of methanol:water:ammonium acetate; 4.0:1.0:0.5 (v/v/v). This system was found to give compact and dense spots for both itopride hydrochloride (Rf value of 0.55±0.02) and pantoprazole sodium (Rf value of 0.85 ± 0.04). Densitometric analysis of both drugs was carried out in the reflectance-absorbance mode at 289 nm. The linear regression analysis data for the calibration plots showed a good linear relationship with R2=0.9988± 0.0012 in the concentration range of 100-400 ng for pantoprazole sodium. Also, the linear regression analysis data for the calibration plots showed a good linear relationship with R2=0.9990±0.0008 in the concentration range of 200-1200 ng for itopride hydrochloride. The method was validated for specificity, precision, robustness and recovery. Statistical analysis proves that the method is repeatable and selective for the estimation of both the said drugs. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating method.

Efficacy of itopride in functional dyspepsia patients overlapping constipation-predominant irritable bowel syndrome / 中华消化杂志

Objective To assess the efficacy of itopride on treatment of patients with functional dyspepsia (FD) overlapping constipation-predominant irritable bowel syndrome (C-IBS). Methods Patients who met criteria for FD and FD overlapping C-IBS were randomly assigned into FD treatment group (group A), FD control group (group B), FD overlapping C-IBS treatment group (group C) and FD overlapping C-IBS control group (group D). The patients in group A and group C received 100 mg of itopride 3 times daily for 8 weeks. Dyspeptic symptoms including abdominal pain, bloating, early satiety and constipation, were evaluated before and after treatment. Ultrasonic monitoring of gastric emptying function was performed in group A and group C before and two weeks after treatment.ResultsThe symptoms of FD were relieved in both group A and group C (P<0.05), while better results were shown in group C. The significant improvement of constipation was seen in group A and group C. Besides, after medication, gastric emptying was improved in group A and group C in comparison with group B and group D. Conclusion Itopride is an effective therapeutic option in the treatmentping of patients with overlapping of FD and C-IBS.

Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats / 中南大学学报(医学版)

Objective To determine the effect of prokinetic agents such as domperidone, mo-sapride, clarithromycin, and itopride on the electrical activity of the stomach and duodenum in SD rats, and also to explore the mechanism. Methods The organism functional experiment system BL-420E was used to record the myoelectrical activity in the stomach and duodenum of SD rats in all groups using domperidone, mosapride, itopride, clarithromycin, and physiological saline on the inter-digestive phase. The effect of the prokinetic agents on the amplitude and freqency of gastric and duo-denal electromyologram in the SD rats was compared. The antagonists such as atropine, phento-lamine, and propranolol were added to investigate the mechanism of action with all prokinetic agents. Results All prokinetic agents increased the amplitude and frequency of gastric and duodenal fast waves in the SD rats (P<0.05). The effect of itopride was the most obvious among the 3 groups (P<0.05), and clarithromycin had the weakest effect (P<0.05). The amplitude and frequency of gastric and duodenal fast waves in the SD rats in the groups of clarithromycin, domperidone, mosa-pride, itopride, and physiological saline were inhibited by atropine (P<0.05) , but not by phento-lamine and propranolol. Conclusion Itopride, mosapride, domperidone, and clarithromycin can in-crease the amplitude and frequency of gastric and duodenal fast waves in the SD rats. The mechanism may be related to cholinergic receptors, but not adrenergic receptors.

Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro

PURPOSE: Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS: The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10cm with 2-cm intervals. RESULTS: In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6)M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9)M). Dopamine (10(-8)M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6)M). Dopamine (10(-8)M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION: Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.

Meta-analysis on Itopride vs. Domperidone in the Treatment of Functional Dyspepsia / 中国药房

OBJECTIVE:To review the curative efficacy and safety of itopride vs. domperidone in the treatment of functional dyspepsia(FD). METHODS:Randomized controlled trails(RCTs)of itopride vs. domperidone in the treatment of FD were enrolled and retrieved from Cochrane Library,PubMed,EMBASE,SCI,CBM,CNKI,VIP and Wanfang Database. Other retrieval was carried out by hand. Methodological quality evaluation and meta-analysis of RCTs were carried out. RESULTS:Of total 18 RCTs enrolled,11 RCTs were graded B and 7 RCTs graded C. Itopride group were superior to domperidone group in respect of total response rate,the relief rate of nausea,abdominal distention,belching,vomiting,epigastric pain and sour regurgitation. There was no statistical significance. The incidence of ADR in itopride group was lower than in domperidone group. There was no statistical significance in difference between two groups. The relief rate of anorexia and early satiety in itopride group were superior to domperidone group. Statistical significance was noted in difference between two groups. CONCLUSION:Recent study shows itopride has better effect than domperidone on FD,which should be confirmed by high quality study.

The Effect of Itopride, a New Prokinetic, on Acid Reflux Symptoms and Variables in Patients with GERD / 대한소화관운동학회지

BACKGROUND/AIMS: Itopride is a newly developed prokinetic agent enhancing gastric motility through both antidopaminergic and anti-acetylcholinesterase actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure. METHODS: The effect of itopride on esophageal 24-hour acid reflux variables was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH<4) of more than 5% and mild esophagitis (Savary-Miller grade I, II) by endoscopy. Ambulatory 24-hour pH monitoring and symptom assessment were performed after treatment with itopride 50 mg or 100 mg t.i.d for 4 weeks by a randomization allocation schedule with an open label. RESULTS: In both itopride groups, total symptom scores were decreased after treatment significantly. Itopride 300 mg was significantly more effective than 150 mg in decreasing the total time and total percent time of intraesophageal pH below 4, and DeMeester score. Consequently, no serious adverse effects were reported after administration in both groups. CONCLUSIONS: Itopride 100 mg t.i.d is effective to decrease pathologic reflux in patients with GERD. Therefore, it has a therapeutic potential for this diseases.