z-338 has been researched along with Dyspepsia* in 44 studies
12 review(s) available for z-338 and Dyspepsia
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Current and emerging therapeutic options for the management of functional dyspepsia.
Topics: Abdominal Pain; Benzamides; Dyspepsia; Humans; Postprandial Period; Syndrome; Thiazoles | 2020 |
Prokinetics for functional dyspepsia.
Dyspepsia is a common condition associated with gastrointestinal (GI) disease. Prokinetics are the treatment of choice for functional dyspepsia (FD). However, the role of prokinetics in FD treatment is still controversial.. We conducted a systematic review and meta-analysis of randomised control trials (RCTs) examining the efficacy of prokinetics in the treatment of FD. The primary outcome was overall absence of or improvement of symptoms and symptom scores at the end of treatment. We also evaluated quality of life (QoL) and adverse events as secondary outcomes.. We performed a systematic search of MEDLINE, Embase, the Cochrane Library, and CINAHL, from 1946 until September 2017. RevMan 5.3 was used to calculate pooled risk ratios (RR) of symptoms persisting or without improved QoL or adverse events, mean difference (MD) or standardised mean difference (SMD) of post-treatment symptoms scores, changes of symptom scores, and QoL, when appropriate with 95% confidence intervals (CI), using a random-effects model. Quality of evidence was evaluated using GRADE methodology.. We included studies that were parallel group RCTs comparing one prokinetic with either placebo or another prokinetic of the same or different class for the treatment of FD. Studies involved adults who presented with dyspepsia symptoms and who had negative or insignificant findings on endoscopy as well as no other organic and metabolic disorders. Studies only including participants with primarily reflux or heartburn symptoms were excluded.. Two review authors independently assessed study eligibility, study quality and performed data extraction.. From an initial 1388 citations, we identified 43 studies in 40 papers. Of those, 29 studies with 10,044 participants compared six prokinetics with placebo for the outcome of absence of symptoms or symptom improvement. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR of remaining dyspeptic = 0.81, 95% CI 0.74 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) =7, very low-quality evidence) with considerable heterogeneity; I. Due to low, or very low, quality of evidence, we are unable to say whether prokinetics are effective for the treatment of functional dyspepsia . We are uncertain which of the individual prokinetic drugs is the most effective as well as whether prokinetics can improve quality of life. Apart from cisapride, prokinetics are well-tolerated. Good quality RCTs are needed to verify the efficacy of prokinetics. Topics: Benzamides; Benzyl Compounds; Cisapride; Domperidone; Dyspepsia; Erythromycin; Gastrointestinal Agents; Humans; Indoles; Morpholines; Numbers Needed To Treat; Quality of Life; Randomized Controlled Trials as Topic; Thiazoles | 2018 |
Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis.
Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD.. Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL.. In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27-6.06), mosapride (OR: 1.99, 95% credible interval: 0.87-4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92-4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29-6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43-6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07-1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04-2.18).. Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Bayes Theorem; Benzamides; Benzyl Compounds; Comparative Effectiveness Research; Domperidone; Dyspepsia; Female; Gastrointestinal Agents; Humans; Male; Metoclopramide; Middle Aged; Morpholines; Network Meta-Analysis; Odds Ratio; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Trimebutine; Young Adult | 2017 |
Emerging treatments in neurogastroenterology: Acotiamade, a novel treatment option for functional dyspepsia.
Acotiamide hydrochloride (Z-338) is a new therapeutic agent for functional dyspepsia (FD). In 2013, the use of acotiamide was approved by the Japanese health insurance system.. The aim of this review is to summarize the present staus of basic and clinical approach to acotiamide for the treatment of functional dyspepsia. The agent inhibits acetylcholinesterase in vitro and enhances muscle motility ex vivo. In phase-II studies, 100 mg three times daily (t.i.d.) was determined to be the optimal dose for the treatment of FD. In phase-III studies, overall treatment efficacy (OTE) was significantly better in the acotiamide group (52.2%) than in the placebo group (34.8%). However, the mechanism of its efficacy needs to be further elucidated. Acotiamide effectively improved FD symptoms, particularly postprandial distress syndrome symptoms, without causing major adverse effects. Topics: Benzamides; Cholinesterase Inhibitors; Dyspepsia; Gastroenterology; Gastrointestinal Agents; Humans; Postprandial Period; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome | 2016 |
Emerging drugs for functional dyspepsia.
Functional dyspepsia (FD) is a relatively common gastrointestinal clinical condition that remains poorly understood. Controversies remain regarding the definition, pathophysiology and optimum treatment. The current treatment of FD is limited and no established regimen is available.. Recent advances have improved our understanding of the pathophysiology of the disease and have led to the development of newer tailored therapies. Novel agents such as the motilin receptor agonist camicinal and the muscarinic M1 and M2 receptor antagonist acotiamide appear promising; however, the need for a safe and efficacious treatment remains largely unmet. This review describes the currently available management options for FD and critically evaluates emerging therapies.. The optimal treatment for FD is yet to be determined. A proton pump inhibitor or a prokinetic agent constitutes primary treatment. Helicobacter pylori testing and eradication is recommended. Based on currently available data, acotiamide appears promising, particularly in postprandial distress syndrome. Further large-scale multicentered trials are required to define the duration of treatment and the side-effect profile. Topics: Benzamides; Drug Design; Dyspepsia; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Postprandial Period; Proton Pump Inhibitors; Thiazoles | 2015 |
[Pharmacological and clinical profile of acotiamide hydrochloride hydrate (Acofide(®) Tablets 100 mg), a novel therapeutic agent for functional dyspepsia (FD)].
Topics: Administration, Oral; Animals; Benzamides; Cholinesterase Inhibitors; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Models, Animal; Dyspepsia; Gastric Emptying; Gastrointestinal Motility; Humans; Tablets; Thiazoles; Treatment Outcome | 2014 |
Evaluation of acotiamide for the treatment of functional dyspepsia.
The treatment for functional dyspepsia (FD) (indigestion) remains unsatisfactory. Acotiamide is a new prokinetic that has been recently approved and used in Japan for the treatment of FD.. This review introduces the pharmacodynamics, pharmacokinetics and efficacy data from current clinical trials from literature sourced using the PubMed search tools. Future principles for developing drugs and designing clinical trials to test them for treating FD are also discussed.. Acotiamide can contribute to the treatment of the specific subset of symptoms defined as postprandial FD by reducing the impaired fundic relaxation and accommodation after eating. The agent has the added benefit of a very good safety profile. Topics: Animals; Benzamides; Clinical Trials as Topic; Drug Approval; Drug Design; Dyspepsia; Humans; Japan; Postprandial Period; Thiazoles | 2014 |
Efficacy and safety of acotiamide for the treatment of functional dyspepsia: systematic review and meta-analysis.
There are no treatments with established efficacy for this disorder so far.. To systematically review the efficacy of acotiamide in the treatment of patients with FD.. We searched main electronic databases through November 2013. RCTs evaluating the efficacy of acotiamide versus placebo in FD patients were included. Pooled risk ratio (RR) with 95% confidential interval (CI) was calculated.. Six publications including seven RCTs were eligible for inclusion. The summary RR of overall improvement of FD symptoms in patients receiving acotiamide versus placebo was 1.29 (95% CI, 1.19-1.40, P < 0.00001; I(2) = 15%). Acotiamide improved the symptoms of patients with postprandial distress syndrome (PDS) (RR, 1.29; 95% CI, 1.09-1.53, P = 0.003; I(2) = 0%), and the summary RR for patients with epigastric pain syndrome (EPS) was 0.92 (95% CI, 0.76-1.11, P = 0.39; I(2) = 0%). Acotiamide showed a significantly beneficial effect on the elimination of some individual FD symptoms compared with placebo. Adverse events were not significantly different between acotiamide and placebo groups. Subgroup analyses suggested that acotiamide 100 mg three times daily (tid) showed consistent efficacy not only for the overall improvement but also for the elimination of some individual symptoms in FD patients.. Acotiamide has the potential to improve the symptoms of patients with FD, particularly of patients with PDS, without major adverse effects. The dosage of acotiamide 100 mg tid might be the appropriate dose in the treatment of FD. Topics: Benzamides; Dose-Response Relationship, Drug; Dyspepsia; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Thiazoles | 2014 |
Dyspepsia.
Dyspepsia affects up to 40% of the general population and significantly reduces quality of life. A small proportion of patients have peptic ulcer disease as cause and this can be treated empirically with Helicobacter pylori eradication therapy in those that are infected. Approximately 20% have gastro-oesophageal reflux disease and this can be effectively treated with proton pump inhibitor therapy. Patients who remain symptomatic may warrant an endoscopy, but most will have functional dyspepsia. Treatment of functional dyspepsia remains a challenge.. Recent large randomized trials suggest tricyclic antidepressant therapy may be effective in functional dyspepsia. A phase III randomized controlled trial reports that a new prokinetic, acotiamide, reduces dyspepsia symptoms in functional dyspepsia patients. There are also preliminary data that suggest buspirone, a drug that promotes gastric accommodation, is also effective in functional dyspepsia. There are also data to suggest that functional dyspepsia is caused by subtle manifestations of inflammation in the upper gastrointestinal tract, possibly caused by food sensitivity or a change in gut flora.. The initial management of dyspepsia is well established, but managing those with continued symptoms is a challenge. Antidepressants and newer gastric motility agents show promise. Targeting the diet and gut microbiome is another area for future research in functional dyspepsia. Topics: Antidepressive Agents, Tricyclic; Benzamides; Diet; Dyspepsia; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Peptic Ulcer; Probiotics; Thiazoles | 2013 |
Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome.
Functional dyspepsia (FD) is a highly prevalent condition with major socioeconomic and healthcare impact. To date, no pharmacological treatment for FD has been approved. The Rome consensus proposed to subdivide FD into postprandial distress syndrome (PDS), characterized by meal-related symptoms and epigastric pain syndrome, characterized by pain and burning. Acotiamide (Z-338 or YM443) is a new drug, developed for the treatment of FD. Acotiamide enhances acetylcholine release from enteric neurons through muscarinic receptor antagonism and acetycholinesterase inhibition, thereby enhancing gastric emptying and gastric accommodation. Acotiamide was evaluated in FD in clinical studies in Europe, Japan and the USA, beneficial effects were observed for the PDS symptoms of postprandial fullness and early satiation, with a dose of 100 mg three-times a day. A 4-week placebo-controlled Phase III study in PDS patients in Japan confirmed efficacy of acotiamide in relieving postprandial fullness, early satiation and upper abdominal bloating. Topics: Animals; Benzamides; Clinical Trials as Topic; Dyspepsia; Humans; Postprandial Period; Thiazoles; Treatment Outcome | 2012 |
Acotiamide (Z-338, YM443), a new drug for the treatment of functional dyspepsia.
Functional dyspepsia (FD) is a highly prevalent condition with a major impact on quality of life and high socio-economic and healthcare costs. To date, no treatment of established efficacy in FD is available. Acotiamide (Z-338 or YM443) is a new drug under development for the treatment of FD.. Acotiamide is a gastroprokinetic drug that enhances acetylcholine release in the enteric nervous system via muscarinic receptor antagonism and acetycholinesterase inhibition. In conscious rats and dogs, acotiamide enhanced gastric contractility and accelerated delayed gastric emptying. Although in healthy volunteers acotiamide did not affect gastric emptying, gastric emptying and gastric accommodation were enhanced in FD. Acotiamide was evaluated in FD in several clinical studies in different countries and these are supportive of a symptomatic benefit. The beneficial effect is most consistently found with the 100 mg dose (three times a day) and primarily involves the postprandial distress syndrome symptoms of postprandial fullness, early satiety and upper abdominal bloating. The mechanism underlying the symptomatic benefit with acotiamide is not fully established but may involve enhanced gastric accommodation and increased gastric emptying.. Compared to placebo, no adverse events have been reported in the current short-term studies, while acotiamide seems efficacious for treating postprandial distress syndrome symptoms in FD patients. Topics: Animals; Benzamides; Clinical Trials as Topic; Dyspepsia; Gastric Emptying; Humans; Stomach; Thiazoles | 2011 |
Acotiamide (Z-338) as a possible candidate for the treatment of functional dyspepsia.
Acotiamide hydrochloride is a novel upper gastrointestinal (GI) motility modulator and stress regulator currently being developed for the treatment of functional dyspepsia (FD). The mechanism underlying the enhancement of GI motility by this agent has been proposed to be based on its muscarinic antagonism and inhibitory effects on acetylcholinesterase activity. Pathophysiological studies showed that acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both normal gastric emptying and feeding in intact animals, indicating that acotiamide exerted effects only on the impaired gastric emptying and feeding behavior. According to the clinical pilot study in Europe, acotiamide, at the dose of 100 mg t.i.d., showed to improve the symptoms and quality of life of patients with FD, indicating the need for larger scale symptomatic studies on the efficacy of acotiamide in patients with FD. The recent phase II studies conducted in Japan presented in this issue of the journal also confirmed that acotiamide, at the optimal dose of 100 mg, has potential therapeutic efficacy, especially for meal-related FD symptoms. Although a phase III study is on going, acotiamide is now expected as a novel treatment option for FD. Topics: Animals; Benzamides; Dyspepsia; Humans; Randomized Controlled Trials as Topic; Thiazoles | 2010 |
12 trial(s) available for z-338 and Dyspepsia
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Effects of acotiamide on functional dyspepsia patients with heartburn who failed proton pump inhibitor treatment in Japanese patients: A randomized, double-blind, placebo-controlled crossover study.
Functional dyspepsia (FD) and non-erosive reflux disease (NERD) are gastrointestinal disorders that often overlap. In this randomized, double-blind, placebo-controlled crossover study, the effects of adding acotiamide to treatment with proton pump inhibitors (PPI) were investigated in FD patients with heartburn who failed PPI treatment, corresponding to PPI-resistant NERD.. The subjects included 16 FD patients with heartburn who failed PPI treatment, and they were administered acotiamide or a placebo for 28 days. After suspending medication for 28 days, the trial drug and placebo were crossed over and administered for 28 days. Before the study began and after each administration period, high-resolution impedance manometry (HRiM) was performed, and the modified frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire was administered.. Postprandial fullness in the FD assessment and all modified FSSG items were significantly lower in the acotiamide group than in the placebo group. Esophagogastric junction pressure was significantly higher in the acotiamide group. The distal contractile integral (DCI) pressure and the highest DCI pressure both increased significantly in the acotiamide group. Moreover, in the acotiamide group, the frequency of abnormal primary peristalsis decreased to normal levels; complete bolus transit (CBT), an indicator of esophageal clearance, increased; and CBT time decreased.. Acotiamide was considered to improve upper gastrointestinal functions not only in the stomach but also in the esophagus. Adding acotiamide to PPI therapy appears to improve upper abdominal symptoms in FD patients with heartburn who failed PPI treatment. Topics: Adult; Aged; Asian People; Benzamides; Cross-Over Studies; Double-Blind Method; Dyspepsia; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Male; Middle Aged; Thiazoles | 2020 |
Therapy of gastroesophageal reflux disease and functional dyspepsia overlaps with symptoms after usual-dose proton pump inhibitor: Acotiamide plus usual-dose proton pump inhibitor versus double-dose proton pump inhibitor.
Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) often coexist or overlap. In this study, the efficacy of acotiamide in combination with a standard dose of rabeprazole for GERD and FD was compared with that of a double dose of rabeprazole.. Patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose proton pump inhibitor (PPI) for ≥ 8 weeks were randomized into two groups and received either acotiamide 300 mg/day + rabeprazole 10 mg/day or rabeprazole 20 mg/day for 4 weeks. Efficacy was assessed by reductions in symptom scores using the Izumo scale questionnaire and modified F-scale questionnaire.. As the primary endpoint, three upper gastrointestinal symptoms (heartburn, epigastralgia, and epigastric fullness) were reduced by ≥ 50% in 40.8% and 46.9% of patients in the combination and PPI double-dose groups, respectively, with no significant difference between the two groups. Essentially similar results were obtained for the modified F-scale questionnaire. No serious adverse events were noted.. Acotiamide 300 mg/day in combination with rabeprazole 10 mg/day or rabeprazole 20 mg/day relieved symptoms in patients with overlap between GERD and FD experiencing heartburn and epigastric fullness symptoms after standard-dose PPI for ≥ 8 weeks, and the efficacies did not differ between the two treatments. The combination therapy may be an alternative option for persistent symptoms in these patients. Topics: Aged; Benzamides; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Dyspepsia; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Rabeprazole; Surveys and Questionnaires; Thiazoles; Time Factors; Treatment Outcome | 2018 |
Long-term safety and efficacy of acotiamide in functional dyspepsia (postprandial distress syndrome)-results from the European phase 3 open-label safety trial.
Acotiamide is a novel acetylcholinesterase inhibitor for treatment of postprandial distress syndrome (PDS) symptoms of functional dyspepsia (FD). This European phase 3 open-label safety trial has been conducted to evaluate the long-term safety of acotiamide and explore the efficacy of acotiamide on PDS symptoms using the validated LPDS, quality of life using SF-36 and SF-NDI, and work productivity using WPAI.. FD-PDS patients (defined by ROME III criteria) aged ≥18 years with active PDS symptoms and without predominant overlapping symptoms of epigastric pain syndrome and related disorders were enrolled to receive 100 mg acotiamide three times daily for 1 year. Patients' safety profile and efficacy of acotiamide were monitored.. The majority of patients (81.6%) maintained exposure to acotiamide for >50 weeks, with a mean duration of 320.3 days. No specific clinically significant safety concerns have been shown, with no deaths, treatment-related severe/serious adverse events, or any clinically significant laboratory test results. Although being an open-label trial, acotiamide showed a change in severity larger than the minimum clinically important difference at weeks 1 and 2 for postprandial fullness and early satiation (meal-related symptoms), and showed improvement of quality of life and work productivity from the first measurement (at week 12) up to 1 year.. The long-term safety of acotiamide treatment was confirmed. A clinically important change for PDS symptoms, QoL, and work productivity was suggested; however a controlled trial is required to confirm this hypothetic efficacy of acotiamide. (NCT01973790). Topics: Adult; Benzamides; Dyspepsia; Europe; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Postprandial Period; Thiazoles; Time Factors; Treatment Outcome | 2018 |
A Randomized, Double-Blind, Pilot Study of the Effect of Famotidine on Acotiamide Treatment for Functional Dyspepsia.
Acotiamide, a prokinetic drug, is used to treat functional dyspepsia (FD), especially postprandial distress syndrome (PDS). However, a treatment for FD patients with PDS and/or epigastric pain syndrome (EPS) has not been established. We investigated the efficacy of famotidine in combination with acotiamide for FD.. Fifty blindly randomized FD patients received placebo with acotiamide, or famotidine with acotiamide, for 4 weeks. Treatment efficacy was assessed by overall treatment effects (OTE), total, PDS and EPS symptom scores, and impairment of quality of life (QOL).. After OTE assessment, patients who felt affected by treatment comprised 40.9 and 57.9% of famotidine and placebo groups, respectively, after 4 weeks' treatment, with no significant difference between groups. A significant decrease was seen in total, PDS, and EPS symptom scores, and in QOL impairment, after 4 weeks' treatment compared with pretreatment scores for famotidine and placebo groups, but was not observed between groups. The proportion of patients showing a ≥50% decrease in EPS symptom scores was greater in the famotidine than that in the placebo group for every observation point, with the greatest difference observed after 2 weeks' treatment.. The effectiveness of famotidine and acotiamide combination therapy in FD was similar to the effectiveness of acotiamide therapy alone. Topics: Abdominal Pain; Adult; Benzamides; Cholinesterase Inhibitors; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Dyspepsia; Famotidine; Female; Histamine H2 Antagonists; Humans; Male; Middle Aged; Pilot Projects; Placebos; Postprandial Period; Proton Pump Inhibitors; Quality of Life; Thiazoles; Treatment Outcome | 2017 |
A double-blind placebo controlled study of acotiamide hydrochloride for efficacy on gastrointestinal motility of patients with functional dyspepsia.
Acotiamide is widely used to improve symptoms in patients with functional dyspepsia (FD) in multiple large-scale clinical studies, but there are few reports about the drug's mechanism of action. The aim of this study was to assess the effects of acotiamide on gastric accommodation and gastric emptying, gastrointestinal symptoms, and health-related quality of life (HR-QOL) in a placebo-controlled study.. We conducted a randomized, double-blind placebo-controlled study. Fifty Japanese FD patients were randomly assigned to either placebo (n = 25) or acotiamide 100 mg × 3/day for 2 weeks (n = 25). At baseline and at 2 weeks of treatment, we evaluated the patients' gastric motility using scintigraphy to determine the accommodation and emptying values, gastrointestinal symptom rating scale (GSRS), HR-QOL (SF-8), and anxiety and depression scale (HADS).. Four patients failed to complete the medication regimen and were omitted from analysis; data from 24 placebo patients and 22 acotiamide patients were analyzed. Acotiamide significantly increased gastric accommodation compared to the placebo (p = 0.04 vs. p = 0.08; respectively). Acotiamide significantly accelerated gastric emptying (50 % half-emptying time) (p = 0.02 vs. p = 0.59). Acotiamide significantly improved the total GSRS scores compared to placebo (p = 0.0007 vs. p = 0.14). HR-QOL did not differ significantly between the two groups, but acotiamide significantly improved the HADS anxiety score compared to placebo (p = 0.04 vs. p = 0.20).. Our placebo-controlled study demonstrated that acotiamide significantly increased both gastric accommodation and gastric emptying in Japanese FD patients. Acotiamide also improved the patients' dyspeptic symptoms and anxiety score. Clinical Trials Registry no: UMIN000013544. Topics: Adult; Aged; Anxiety; Benzamides; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychometrics; Quality of Life; Radionuclide Imaging; Severity of Illness Index; Stomach; Thiazoles; Treatment Outcome | 2017 |
Improvement of meal-related symptoms and epigastric pain in patients with functional dyspepsia treated with acotiamide was associated with acylated ghrelin levels in Japan.
The aim of this study is to clarify whether acotiamide and rabeprazole combination therapy can improve clinical symptoms, gastric emptying, and satisfaction with treatment in functional dyspepsia (FD) patients more effectively than acotiamide or rabeprazole monotherapy alone. We also aimed to determine whether acotiamide affects these changes via its effect on gastric emptying and appetite-related hormones such as ghrelin.. We used Rome III criteria to evaluate upper abdominal symptoms and anxiety by the State-Trait Anxiety Inventory (STAI). Gastric motility was evaluated by the (13) C-acetate breath test. Eighty-one FD patients were treated with acotiamide (300 mg/day) (n = 35), acotiamide (300 mg/day) and rabeprazole (10 mg/day) (n = 28), or rabeprazole (10 mg/day) (n = 18) for a period of 4 weeks and followed after 4 weeks of no treatment. Adenocorticotropic hormone (ACTH), cortisol, leptin and ghrelin levels were measured in all FD patients.. Acotiamide and rabeprazole combination therapy significantly improved postprandial distress syndrome (PDS)-like symptoms (p = 0.018, p = 0.04 and p = 0.041, respectively) and epigastric pain (p = 0.024) as wells as STAI-state scores (p = 0.04) compared to rabeprazole monotherapy. Both acotiamide monotherapy, and acotiamide taken in combination with rabeprazole, significantly (p = 0.001 and p = 0.02, respectively) improved satisfaction with treatment, compared to rabeprazole monotherapy. Acotiamide and rabeprazole combination therapy had no significant effect on ACTH and cortisol levels in FD patients. Of interest, acotiamide monotherapy, and acotiamide and rabeprazole combination therapy, significantly (p < 0.0001 and p = 0.018, respectively) increased acylated ghrelin/total ghrelin ratios and significantly (p = 0.04) improved impaired gastric emptying compared to rabeprazole monotherapy.. Further studies are warranted to clarify how acotiamide treatment improves clinical symptoms in FD patients. Topics: Abdominal Pain; Acylation; Adolescent; Adult; Aged; Aged, 80 and over; Benzamides; Biomarkers; Drug Therapy, Combination; Dyspepsia; Female; Gastrointestinal Agents; Ghrelin; Humans; Japan; Male; Meals; Middle Aged; Postprandial Period; Prospective Studies; Rabeprazole; Thiazoles; Treatment Outcome; Young Adult | 2016 |
Efficacy of acotiamide in combination with esomeprazole for functional dyspepsia refractory to proton-pump inhibitor monotherapy.
Functional dyspepsia (FD) is a gastroduodenal disorder that presents as postprandial fullness, early satiation, or epigastric burning despite no evidence of a structural disease. Proton pump inhibitors (PPIs) are often the first choice for treating FD. However, some patients need additional medication because of residual symptoms despite a certain level of benefit from the PPI. For these patients, a combination of PPI and other agents has a possibly more beneficial effect than changing their medication. This study aimed to evaluate the efficacy of an initial PPI followed by combination therapy with PPI and acotiamide in FD patients with residual symptoms after an initial PPI. We enrolled 105 patients who started an initial PPI (20 mg of esomeprazole once a day). Twenty-three patients with residual symptoms received 100 mg of acotiamide, a cholinesterase inhibitor, three times a day with esomeprazole as a combination therapy for 2 weeks. The symptoms were evaluated using the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSG). Eighteen of 23 patients (78%) achieved an overall improvement in symptoms. Almost all FD-related symptoms statistically improved after the combination therapy, with an improvement in the mFSSG score relevant to the postprandial distress syndrome and epigastric pain syndrome. The symptoms improved regardless of age, sex, and the pre-combination therapy score of the mFSSG. Our findings suggest that the combination therapy of acotiamide and PPI may be effective in selected FD patients with insufficient improvement with an initial PPI. However, well-designed trials are required to confirm the efficacy. Topics: Benzamides; Drug Resistance; Drug Therapy, Combination; Dyspepsia; Esomeprazole; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proton Pump Inhibitors; Thiazoles; Treatment Outcome | 2014 |
A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia.
To determine the efficacy of acotiamide, an acetylcholinesterase inhibitor, in patients with functional dyspepsia (FD) in a 4-week trial.. A multicentre, randomised, placebo-controlled, parallel-group, phase III trial was carried out, in which patients with FD received 100 mg of acotiamide or placebo three times a day for 4 weeks, with 4 weeks post-treatment follow-up. The primary efficacy end points were global assessment of overall treatment efficacy (OTE) and elimination rate of all three meal-related symptoms (postprandial fullness, upper abdominal bloating and early satiation), as derived from daily diaries. Secondary efficacy end points were individual symptom scores and quality of life. Adverse events were monitored.. 52.2% of those receiving acotiamide and 34.8% in the placebo group (p<0.001) were classified as responders according to a global assessment of OTE. Over 4 weeks, the elimination rate for all three meal-related symptoms was 15.3% among patients receiving acotiamide compared with 9.0% in the placebo group (p=0.004). The significant benefit of acotiamide over placebo in OTE and elimination rate was maintained during the 4 week post-treatment follow-up. All other secondary efficacy end points, including quality of life, were significantly improved with 100 mg of acotiamide as compared with placebo. The number needed to treat was 6 for OTE and 16 for symptom elimination rate. The incidence of adverse events was similar between the acotiamide group and placebo group and no significant cardiovascular effects due to treatment were seen.. Over 4 weeks, acotiamide significantly improved symptom severity and eliminated meal-related symptoms in patients with FD.. http://ClinicalTrials.gov number, NCT00761358. Topics: Adult; Benzamides; Cholinesterase Inhibitors; Double-Blind Method; Dyspepsia; Eating; Female; Humans; Male; Postprandial Period; Thiazoles; Time Factors; Treatment Outcome | 2012 |
Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography.
Improvement in subjective symptoms has been reported in functional dyspepsia (FD) patients administered with acotiamide. Improvement was confirmed in meal-related symptoms, such as postprandial fullness, upper abdominal bloating, and early satiety. We examined the mechanism underlying the effects of acotiamide on gastric accommodation reflex (GAR) and gastroduodenal motility in FD patients.. Thirty-four FD patients (mean age, 40.4 years) were examined ultrasonographically before and after 14-18 days of acotiamide (100 mg t.i.d.) or placebo administration. To assess GAR, expansion rate in cross-sectional area of the proximal stomach was measured after every 100-mL ingestion, using a straw, of up to 400 mL of a liquid meal (consommé soup, 13.1 kcal; 400 mL) in a supine position. Next, we measured gastric emptying rate (GER), motility index (MI, antral contractions), and reflux index (RI, duodenogastric reflux) to assess gastroduodenal motility. Patients also completed a survey based on the seven-point Likert scale both before and after drug administration.. Of the 37 cases, 19 and 18 were administered with acotiamide and placebo A respectively, significant difference was observed in GAR between the acotiamide and placebo groups (21.7%vs 4.4%) after 400 mL ingestion. GER significantly accelerated after treatment in the acotiamide group (P = 0.012), no significant differences were observed in MI and RI between the two groups. Improvement rates were 35.3 and 11.8% for the acotiamide and placebo groups.. Acotiamide significantly enhances GAR and GER in FD patients. Acotiamide may have therapeutic potential for FD patients. Topics: Adult; Aged; Benzamides; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Male; Middle Aged; Postprandial Period; Stomach; Supine Position; Thiazoles; Treatment Outcome; Ultrasonography | 2012 |
A long-term study of acotiamide in patients with functional dyspepsia: results from an open-label phase III trial in Japan on efficacy, safety and pattern of administration.
This long-term 48-week study of acotiamide was carried out to investigate the efficacy, safety and administration pattern in patients with functional dyspepsia (FD).. This was a multicenter, open-label, single-arm, long-term phase III study in which patients with FD were given acotiamide, 100 mg t.i.d., for 48 weeks. The two major efficacy endpoints were global overall treatment efficacy (OTE) and the elimination rate of three cardinal symptoms (i.e. postprandial fullness, early satiation and upper abdominal bloating), which were evaluated weekly and daily by the patients, respectively. The long-term administration patterns were investigated by following the patients based on cessation and readministration criteria.. Efficacy was analyzed in 405 patients. The OTE improvement rate was 26.1% at week 1 and increased with time. It was 60.6% at week 8 and subsequently maintained. Similarly, the symptom elimination rate increased up to week 8. Many patients who met the cessation criterion achieved remission of FD symptoms after experiencing dose interruption and readministration. The incidence rate of adverse drug reactions was 11.5% and most of the adverse drug reactions were mild in severity except increased ALT in 1 patient.. FD symptoms were controlled by intermittent administration of acotiamide even in patients with relapsing FD. Topics: Abdominal Pain; Adult; Benzamides; Dyspepsia; Female; Humans; Male; Middle Aged; Muscarinic Agonists; Postprandial Period; Satiation; Sensation; Thiazoles; Time Factors; Treatment Outcome; Young Adult | 2011 |
Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal dosage.
Acotiamide is a selective acetylcholinesterase inhibitor and enhances the actions of cholinergic neurons localized in the stomach.. The present two studies were conducted to examine the optimal dosage of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia (FD) in Japan.. The improvement rate of 'subjects global assessment of overall treatment efficacy (OTE)' at the final evaluation was approximately 10% higher in the acotiamide 100 mg group than that in the placebo group with good reproducibility though there was no significant differences at primary endpoint. The elimination rate of postprandial fullness in the acotiamide 100 mg group was significantly higher compared to placebo group. In addition, the post hoc analysis showed that in patients whose main complaints are meal-related symptoms such as postprandial fullness, upper abdominal bloating and/or early satiety, the improvement rate of 'OTE' at final evaluation in acotiamide 100 mg group was significantly superior to that in the placebo group.. These results suggest that acotiamide possesses efficacy on FD and more specifically its meal-related symptoms of FD. Topics: Adult; Aged; Benzamides; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Eating; Endpoint Determination; Female; Gastric Emptying; Humans; Male; Middle Aged; Patient Compliance; Satiety Response; Thiazoles; Young Adult | 2010 |
A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia.
Impaired gastric accommodation, hypersensitivity to distension and delayed gastric emptying are major pathophysiological mechanisms in functional dyspepsia (FD). Acotiamide (Z-338) was well-tolerated in healthy volunteers. To determine the effect of three doses of Acotiamide on major pathophysiological mechanisms, symptoms, quality of life (QOL) and safety in functional dyspeptics. A phase IIa, randomized, double-blind, placebo-controlled study (14, 21 and 28 days, respectively, for run-in, study drug administration and follow-up). Gastric accommodation, sensitivity to distension and gastric emptying were assessed by barostat and (13)C breath test, symptoms by daily diary cards and QOL by SF-36. A total of 71 patients were enrolled (62 evaluable). There was no effect on gastric emptying and sensitivity to distension. 300 mg was better than placebo for meal accommodation (P = 0.024). 100 mg was better than placebo at week 2 for upper abdominal bloating (P = 0.001) and overall symptom score (P = 0.022), and at week 3 for bloating (P = 0.008) and heartburn (P = 0.041). 100 mg was also better than placebo for QOL (physical function) (P = 0.003). Acotiamide was safe and well-tolerated in patients with FD. The involved mechanism could at least in part depend on an effect on meal-induced accommodation. 100 mg Acotiamide exhibited the potential to improve FD symptoms and QOL. Further studies are indicated. Topics: Adolescent; Adult; Aged; Benzamides; Breath Tests; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Agents; Humans; Male; Middle Aged; Pilot Projects; Placebos; Quality of Life; Thiazoles; Young Adult | 2009 |
20 other study(ies) available for z-338 and Dyspepsia
Article | Year |
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The Effect of Acotiamide on Nausea as a Symptom of Chronic Nausea and Vomiting Syndrome after Coronavirus Disease 2019.
Chronic nausea and vomiting syndrome (CNVS), one of a functional gastroduodenal disorder, was identified in an 8-year-old girl and a 13-year-old boy who had complained of nausea for more than 4 months following coronavirus disease 2019 (COVID-19) due to normality of their head computed tomography and upper gastrointestinal tract images. The patients' symptoms responded quickly to acotiamide, a medication that is effective for treating functional dyspepsia (FD). Despite being a distinct illness from FD, CNVS is also a functional gastrointestinal disorder, and acotiamide may be just as effective for CNVS following COVID-19 as for FD. Topics: Adolescent; Child; COVID-19; Dyspepsia; Female; Humans; Male; Nausea; Treatment Outcome; Vomiting | 2023 |
Vonoprazan Therapy is as Effective for Functional Dyspepsia without Heartburn as Acotiamide Therapy.
Acid suppression improves dyspepsia symptoms but the efficacy of vonoprazan for functional dyspepsia remains unclear. The aim of this study is to evaluate the effectiveness of vonoprazan therapy for functional dyspepsia without heartburn.. Patients receiving vonoprazan 10 mg once daily or acotiamide 100 mg three times daily for more than one month were included and retrospectively reviewed. Functional dyspepsia was diagnosed based on the ROME IV criteria. Patients with heartburn were excluded. Eighty-five patients were divided into vonoprazan (n=48) and acotiamide (n=37) groups.. There were no significant differences at baseline between the vonoprazan and acotiamide groups. The functional dyspepsia score significantly improved in both groups (p<0.001). The degree of score reduction (55% vs 59%, p=0.559) and the resolution rates (21% vs 30%, p=0.345) were similar. Epigastric pain and postprandial distress scores were significantly improved in both groups, and the degree of improvement of each score was similar. Constipation and diarrhea scores were significantly improved in both groups, and the degree of improvement similar.. These preliminary results suggest that vonoprazan is effective for the treatment of functional dyspepsia without heartburn in the short-term, with results similar to acotiamide therapy. Topics: Dyspepsia; Heartburn; Humans; Retrospective Studies | 2023 |
The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia.
Topics: Animals; Benzamides; Benzyl Compounds; Disease Models, Animal; Dyspepsia; Gastrointestinal Motility; Isothiocyanates; Male; Mice, Inbred Strains; Morpholines; Neostigmine; Panax; Phytotherapy; Plant Extracts; Thiazoles; Wasabia; Zanthoxylum; Zingiberaceae | 2021 |
Identification of the Uptake Transporter Responsible for Distribution of Acotiamide into Stomach Tissue.
The acetylcholinesterase inhibitor, acotiamide, improves gastric motility and is clinically used to treat functional dyspepsia. The present study aimed to identify the transporters involved in the distribution of acotiamide in stomach tissue. Acotiamide uptake by the gastric cancer-derived model cell line, Hs746 T, was Na Topics: Acetylcholinesterase; Benzamides; Biological Transport; Cell Line; Cholinesterase Inhibitors; Dyspepsia; Endothelial Cells; Equilibrative Nucleoside Transport Proteins; Gastric Mucosa; HEK293 Cells; Humans; Muscle, Smooth; Selective Serotonin Reuptake Inhibitors; Stomach; Thiazoles | 2020 |
Timing and Predictors of Recurrence of Dyspepsia Symptoms after Cessation of Acotiamide Therapy for Functional Dyspepsia: A Long-Term Observational Study.
The long-term outcomes of patients after cessation of acotiamide therapy in patients with functional dyspepsia remains unclear. The aim of this study is to investigate the timing and predictors of recurrence of dyspepsia symptoms after cessation of acotiamide therapy for functional dyspepsia.. Seventy patients treated with acotiamide for functional dyspepsia who then ceased treatment were enrolled. Changes in dyspepsia symptoms were evaluated using the Izumo scale, a self-reporting questionnaire of abdominal symptom-related quality of life. Patients were subclassified into epigastric pain, postprandial distress, and overlapped types.. The mean follow-up after cessation of acotiamide was 1.9 years. After cessation of acotiamide, 39 patients (56%) had recurrence. Kaplan-Meier analysis revealed a recurrence-free rate of 51% at 1 year. Predictors of recurrence evaluated with a Cox proportional hazards model showed that overlapped-type dyspepsia and consultation with the treating physician before cessation were identified as significant positive and negative predictors, respectively (p < 0.05). The resumption of acotiamide significantly decreased the score for dyspepsia symptoms at 1 month.. Dyspepsia symptoms recur about one year after cessation of acotiamide therapy. Patients with overlapped-type dyspepsia should be carefully followed after cessation. Patients should consult their treating physician before stopping acotiamide. Topics: Adult; Aged; Benzamides; Dyspepsia; Female; Gastrointestinal Agents; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Patient Outcome Assessment; Proportional Hazards Models; Recurrence; Symptom Assessment; Thiazoles; Time Factors; Withholding Treatment | 2020 |
Camostat Mesilate, Pancrelipase, and Rabeprazole Combination Therapy Improves Epigastric Pain in Early Chronic Pancreatitis and Functional Dyspepsia with Pancreatic Enzyme Abnormalities.
The aims of the study are to clarify the pathophysiological differences among early chronic pancreatitis (ECP), functional dyspepsia with pancreatic (FD-P) enzyme abnormalities and FD patients and to determine whether camostat mesilate, pancrelipase, and rabeprazole triple therapy improve FD symptoms in the ECP patients and FD-P patients in cross-over way.. We enrolled 84 consecutive patients presenting with typical symptoms of FD patients (n = 42), ECP patients (n = 15), and FD-P patients (n = 27). Gastric emptying was assessed by the 13C-acetate breath test. ECP was diagnosed based on the criteria recommended by the Japan Pancreatic Association.. The proportions of female in ECP patients and FD-P were significantly higher compared to that in FD patients. The early phase of gastric emptying in ECP and FD-P patients was significantly disturbed compared to that in FD patients. The primary outcome of this study is that 4 weeks of camostat mesilate, pancrelipase, and rabeprazole triple therapy significantly ameliorated epigastric pain in ECP patients compared to acotiamide and rabeprazole combination therapy.. Although there were no significant differences in pathophysiology between ECP patients and FD-P patients, triple therapy can significantly ameliorate epigastric pain in ECP patients. Further studies will be needed to clarify why triple therapy can improve epigastric pain in ECP patients. Topics: Abdominal Pain; Aged; Benzamides; Drug Therapy, Combination; Dyspepsia; Esters; Female; Gabexate; Gastrointestinal Agents; Guanidines; Humans; Male; Middle Aged; Pancreatitis, Chronic; Pancrelipase; Rabeprazole; Thiazoles; Treatment Outcome | 2019 |
Real-World, Non-Interventional, Observational Study to Evaluate Effectiveness and Tolerability of Acotiamide Hydrochloride Hydrate in Treatment of Functional Dyspepsia.
Functional dyspepsia (FD) is a highly prevalent condition which reduces patients' quality of life (QoL) and imparts a significant economic burden on the healthcare system. Acotiamide is a novel prokinetic agent useful in treatment of FD, and this study evaluated the effectiveness of acotiamide hydrochloride hydrate in management of FD over a 4-week period in a real-world setting.. This study was a prospective, observational, real-world data collection of 132 patients (85 male, 47 female) over 18 years of age diagnosed with FD as per Rome III criteria and treated with acotiamide for 4 weeks at a gastroenterology unit of a medical school in India. Those receiving prokinetics and cholinergic drugs, having any structural lesion on endoscopy, with coexisting irritable bowel syndrome and having heartburn in the past 12 weeks were excluded. Primary outcome was responders based on overall treatment efficacy (OTE) recorded on a seven-point Likert scale for postprandial distress syndrome (PDS; postprandial fullness, early satiety and upper abdominal bloating), epigastric pain syndrome (EPS; upper abdominal pain and upper abdominal discomfort) and associated symptoms (nausea, vomiting and excessive belching) at the end of 2 and 4 weeks. Secondary outcomes were elimination of symptoms of PDS, QoL assessed on the Short-Form Nepean Dyspepsia Index (SFNDI) questionnaire and clinical safety after 2 and 4 weeks.. The responder rates with acotiamide at 2 and 4 weeks were 51.5% and 65.9%, respectively, for PDS. Similarly, the responder rates for EPS were 31.8% and 41.7%, respectively, at 2 weeks and 4 weeks. The responder rates for associated symptoms of nausea, vomiting and excessive belching were respectively 18.2%, 17.4% and 16.7% at 2 weeks and 18.2%, 17.4% and 18.2% at 4 weeks. Symptom elimination rates were 9.8% and 18.9% for postprandial fullness, 12.9% and 22.0% for early satiety, and 18.9% and 24.2% for abdominal bloating at 2 and 4 weeks, respectively. Significant improvement (p < 0.0001) in the SFNDI total scores from 25.91 (5.00) at 2 weeks to 23.76 (4.84) at 4 weeks were found at 4 weeks compared to 2 weeks. A total of 7 (5.30%) patients reported mild adverse events which were dizziness (4), headache (3) and nausea (1).. The current study demonstrates that treatment with acotiamide improves symptoms, QoL and is well tolerated in Indian patients with FD.. Clinical Trial Registry of India, CTRI/2017/11/010421.. Dr. Reddy's Laboratories, India. Topics: Adult; Benzamides; Dyspepsia; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; India; Male; Middle Aged; Prospective Studies; Quality of Life; Thiazoles; Treatment Outcome | 2018 |
Extensive gastric mucosal atrophy is a possible predictor of clinical effectiveness of acotiamide in patients with functional dyspepsia
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Acotiamide is known as an effective agent for functional dyspepsia. However, clinical factors related to its effectiveness have not been fully elucidated, so it is difficult to predict the drug's effectiveness prior to its administration in patients.. The present retrospective study was conducted to examine the relationship between clinical factors and the effectiveness of acotiamide for functional dyspepsia.. The study subjects were 149 patients with functional dyspepsia who were prescribed acotiamide. Based on medical records and clinical factors, including endoscopic findings, the effectiveness of acotiamide was investigated.. Significant clinical factors associated with acotiamide's effectiveness were identified. These included postprandial syndrome, concomitant mental disorder, and extensive gastric mucosal atrophy. On multiple regression analysis, extensive gastric mucosal atrophy showed the strongest relationship with the clinical effectiveness of acotiamide; the other significant factor was concomitant mental disorder.. Although the pathophysiology of the relationship between mucosal atrophy and acotiamide remains uncertain, a decrease in hormonal secretion, such as that of ghrelin, may be a possible mechanism. . Topics: Adult; Aged; Atrophy; Benzamides; Dyspepsia; Female; Gastric Mucosa; Ghrelin; Humans; Male; Middle Aged; Retrospective Studies; Thiazoles | 2017 |
Adherence to an acotiamide therapeutic regimen improves long-term outcomes in patients with functional dyspepsia.
Long-term outcomes in patients with functional dyspepsia remain elusive. Acotiamide, a prokinetic drug, has been available in Japan since 2013. The aim of this study was to assess long-term outcomes in patients with functional dyspepsia treated with acotiamide.. We retrospectively reviewed 79 consecutive patients with functional dyspepsia whose symptoms improved with acotiamide therapy and who were followed for more than one year. All patients underwent esophagogastroduodenoscopy prior to acotiamide therapy. The mean follow-up was 1.9 (range, 1.0-3.3) years. We assessed the patients' symptom severity using the Izumo scale, which reflects changes in various abdominal symptoms.. At one year, dyspepsia symptoms recurred in 25% (20/79) of the patients. In multivariate analysis, severe dyspepsia was significantly associated with increased recurrence (odds ratio [OR] 15.04, 95% confidence interval [CI] 1.73-130.47, p=0.013). Continued use of acotiamide for one year diminished the recurrence of dyspepsia symptoms significantly (OR 0.16, 95%CI 0.04-0.61, p=0.006). The influence of these significant predictors on long-term outcomes was analyzed using the Kaplan-Meier method. Patients with severe dyspepsia before starting acotiamide had significantly more recurrences than those with mild symptoms (p=0.004, log-rank test). Patients who continued acotiamide therapy throughout the follow-up period had significantly fewer recurrences than those who stopped therapy (p<0.001).. Over the long-term, patients with functional dyspepsia have a considerable rate of recurrence of dyspepsia. Severe dyspepsia before treatment increases the recurrence rates, while adherence to an acotiamide therapeutic regimen decreases recurrence rate. Topics: Adult; Aged; Benzamides; Cholinesterase Inhibitors; Dyspepsia; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Severity of Illness Index; Thiazoles; Treatment Outcome | 2017 |
Physiologically-Based Pharmacokinetic and Pharmacodynamic Modeling for the Inhibition of Acetylcholinesterase by Acotiamide, A Novel Gastroprokinetic Agent for the Treatment of Functional Dyspepsia, in Rat Stomach.
Acotiamide, a gastroprokinetic agent used to treat functional dyspepsia, is transported to at least two compartments in rat stomach. However, the role of these stomach compartments in pharmacokinetics and pharmacodynamics of acotiamide remains unclear. Thus, the purpose of this study was to elucidate the relationship of the blood and stomach concentration of acotiamide with its inhibitory effect on acetylcholinesterase (AChE).. Concentration profiles of acotiamide and acetylcholine (ACh) were determined after intravenous administration to rats and analyzed by physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) model containing vascular space, precursor pool and deep pool of stomach.. Acotiamide was eliminated from the blood and stomach in a biexponential manner. Our PBPK/PD model estimated that acotiamide concentration in the precursor pool exceeded 2 μM at approximately 2 h after administration. Acotiamide inhibited AChE activity in vitro with a 50% inhibitory concentration of 1.79 μM. ACh reached the maximum concentration at 2 h after administration.. Our PBPK model well described the profile of acotiamide and ACh concentration in the stomach in the assumption that acotiamide was distributed by carrier mediated process and inhibited AChE in the precursor pool of stomach. Thus, Acotiamide in the precursor pool plays an important role for producing the pharmacological action. Topics: Acetylcholinesterase; Animals; Benzamides; Cholinesterase Inhibitors; Dyspepsia; Gastric Emptying; Gastric Mucosa; Male; Rats; Rats, Sprague-Dawley; Stomach; Thiazoles | 2016 |
Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity in Circular Muscle Strips of Guinea Pig Stomach.
Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinesterase (AChE) activity in stomach homogenate following fundus removal. We also investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor and AChE inhibitor itopride, and representative AChE inhibitor neostigmine. Acotiamide (0.3 and 1 μM) and itopride (1 and 3 μM) significantly enhanced the contraction of gastric body strips induced by electrical field stimulation (EFS), but mosapride (1 and 10 μM) did not. Acotiamide and itopride significantly enhanced the contraction of gastric body and antrum strips induced by acetylcholine (ACh), but not that induced by carbachol (CCh). Neostigmine also significantly enhanced the contraction of gastric body strips induced by ACh, but not that by CCh. In contrast, mosapride failed to enhance contractions induced by either ACh or CCh in gastric antrum strips. Acotiamide exerted mixed inhibition of AChE, and the percentage inhibition of acotiamide (100 μM) against AChE activity was markedly reduced after the reaction mixture was dialyzed. In contrast, itopride exerted noncompetitive inhibition on AChE activity. These results indicate that acotiamide enhances ACh-dependent contraction in gastric strips of guinea pigs via the inhibition of AChE activity, and that it exerts mixed and reversible inhibition of AChE derived from guinea pig stomach. Topics: Acetylcholine; Acetylcholinesterase; Animals; Benzamides; Benzyl Compounds; Carbachol; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Dyspepsia; Guinea Pigs; In Vitro Techniques; Male; Morpholines; Muscle Contraction; Muscle, Smooth; Neostigmine; Stomach; Thiazoles | 2016 |
Distribution of acotiamide, an orally active acetylcholinesterase inhibitor, into the myenteric plexus of rat and dog stomachs.
Acotiamide is the first-in-class drug for the treatment of functional dyspepsia. Although pharmacological and therapeutic actions of acotiamide are thought to be derived from its inhibitory effects on acetylcholinesterase (AChE), whether the concentration of acotiamide at the site of action is sufficient to inhibit AChE remains unclear. Since major site of acotiamide action is thought to be the cholinergic nerve terminals in gastric myenteric plexus, we studied the distribution of [(14)C]acotiamide into gastric myenteric plexus.. Distribution of [(14)C]acotiamide was evaluated using macro- and micro-autoradiography in rats and dogs.. The results of macro-autoradiography showed the concentration of radioactivity was 27.9μM in rat stomach, which was 12 times higher than IC50 of acotiamide for rat AChE. Being different from rats, the distribution of radioactivity in the muscular layer was distinguishable from that in the mucosal layer in dog stomach. The concentration of radioactivity in the muscular layer of dog stomach (1.41μM) was approximately two-times lower than those in the mucosal layer, however, it was approximately 1.2 times higher than IC50 of acotiamide for dog AChE. The results of micro-autoradiography also showed the radioactivity distributed homogenously in the muscular layer of rat stomach, suggesting the concentration of radioactivity around the ganglion of myenteric plexus is similar to that in the muscular layer of stomach.. These findings suggest acotiamide distributes to the myenteric plexus of stomach, a putative site of acotiamide action, with adequate concentrations to inhibit AChE, in both of rat and dog stomachs. Topics: Acetylcholinesterase; Animals; Benzamides; Cholinesterase Inhibitors; Dogs; Dyspepsia; Gastric Mucosa; Male; Myenteric Plexus; Rats; Rats, Sprague-Dawley; Stomach; Thiazoles | 2016 |
Effects of Acotiamide on the Esophageal Motility Function in Patients with Esophageal Motility Disorders: A Pilot Study.
Acotiamide is a newly developed prokinetic drug that is clinically used to treat functional dyspepsia (FD). The objective of this study was to assess the therapeutic effects of acotiamide in patients with esophageal motility disorders (EMDs).. Twenty-nine patients with both symptoms of FD and symptoms suspicious of EMDs were enrolled. Esophageal motility function was evaluated by high-resolution manometry before and after 2 weeks administration of acotiamide (100 mg) 3 times per day.. Twenty-nine patients were diagnosed with achalasia (n = 4), esophagogastric junction outflow obstruction (EGJOO) (n = 6), absent peristalsis (n = 2), distal esophageal spasm (n = 4), frequently failed peristalsis (n = 7), weak peristalsis (n = 2) and 4 of them were found to be normal. An analysis in all 29 patients showed that acotiamide had no effects on based on distal contractile integral (DCI), basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP). Subgroup analysis, however, showed that acotiamide dramatically reduced IRP, from 19.5 (15.1-30.8) to 12.1 (5.6-16.4) mm Hg, and DCI, from 2,517.9 (1,451.0-8,385.0) to 1,872.5 (812.3-5,225.3) mm Hg·cm·s, in the 6 patients with EGJOO.. Acotiamide potentially normalized impaired LES relaxation in patients with EGJOO, while having no effects on normal esophageal motility patterns. Acotiamide may be a promising treatment for EGJOO. Topics: Adult; Aged; Aged, 80 and over; Benzamides; Dyspepsia; Esophageal Motility Disorders; Esophageal Sphincter, Lower; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Japan; Male; Manometry; Middle Aged; Pilot Projects; Single-Blind Method; Thiazoles | 2016 |
The effect of acotiamide on epigastric pain syndrome and postprandial distress syndrome in patients with functional dyspepsia.
The effect of acotiamide on gastrointestinal symptoms is undefined. The aim of this study is to evaluate the effect of acotiamide on abdominal symptoms in patients with functional dyspepsia. We retrospectively reviewed 51 patients treated with acotiamide. We evaluated patient quality of life using the Izumo scale that detects changes in quality of life caused by abdominal symptoms. Acotiamide ameliorated the symptoms of functional dyspepsia at one and three months (improved: 61% vs 80%, p=0.029 and resolved: 17% vs 33%, p=0.069). We then evaluated the effect of acotiamide on epigastric pain syndrome (EPS) (n=33) and postprandial distress syndrome (PDS) (n=41). Acotiamide treatment showed an early effect on rates of improvement (63%) and resolution (42%) of EPS symptoms at one month, maintained up to three months (69% and 39%, respectively). Both rates of improvement and resolution of PDS symptoms showed a significant increase from one month to three months (56% vs 78%, p=0.021 and 17% vs 46%, p=0.004, respectively). The severity of functional dyspepsia symptoms before treatment was significantly associated with failed resolution of functional dyspepsia symptoms (p=0.013). Acotiamide improves and resolves EPS symptoms as well as PDS symptoms. PDS symptoms take longer to resolve than EPS symptoms. J. Med. Invest. 63: 230-235, August, 2016. Topics: Abdominal Pain; Adult; Aged; Benzamides; Dyspepsia; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Postprandial Period; Quality of Life; Retrospective Studies; Syndrome; Thiazoles | 2016 |
[Gastrointestinal motility disorders of functional dyspepsia].
Topics: Benzamides; Dyspepsia; Eating; Gastrointestinal Motility; Humans; Thiazoles | 2014 |
Functional dyspepsia: Glimmers of hope for functional dyspepsia.
Topics: Benzamides; Diet; Disease Management; Dyspepsia; Helicobacter Infections; Humans; Life Style; Psychology; Thiazoles | 2013 |
Acotiamide: first global approval.
Acotiamide (Acofide(®)), an oral first-in-class prokinetic drug, is under global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for the treatment of patients with functional dyspepsia. The drug modulates upper gastrointestinal motility to alleviate abdominal symptoms resulting from hypomotility and delayed gastric emptying. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Unlike other prokinetic drugs that are utilized in the management of functional dyspepsia, acotiamide shows little/no affinity for serotonin or dopamine D2 receptors. Acotiamide is the world's first approved treatment for functional dyspepsia diagnosed by Rome III criteria, with its first approval occurring in Japan. Phase III trials in this patient population are in preparation in Europe, with phase II trials completed in the USA and Europe. This article summarizes the milestones in the development of acotiamide, leading to its first approval for use in patients with functional dyspepsia. Topics: Benzamides; Drug Approval; Dyspepsia; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Thiazoles | 2013 |
New hope for functional dyspepsia?
Topics: Benzamides; Cholinesterase Inhibitors; Dyspepsia; Female; Humans; Male; Thiazoles | 2012 |
Mechanism for distribution of acotiamide, a novel gastroprokinetic agent for the treatment of functional dyspepsia, in rat stomach.
The novel gastroprokinetic agent acotiamide improves gastric motility by inhibiting acetylcholinesterase activity in stomach; however, the mechanism of distribution of acotiamide from blood to stomach has not been clarified. Here, the tissue distribution of acotiamide was investigated in rats. The tissue-to-plasma concentration ratio (K(p,app,in vivo)) for stomach decreased from 4.1 to 2.4 mL/g of tissue at steady state with increasing plasma concentrations, whereas the K(p,app,in vivo) for skeletal muscle was much lower and constant, regardless of the concentration of acotiamide in plasma. In vitro binding to stomach tissue protein exhibited a linear profile, with a predicted K(p,app,in vitro) of 2.2 from free fractions under linear conditions. Therefore, protein binding to stomach tissue might only play a limited role in the stomach distribution of acotiamide. The influx permeability (f (u,b) × PS(inf,app)) in the stomach exhibited dose-dependent saturation at the lowest range of examined blood unbound concentrations of acotiamide, whereas that in skeletal muscle exhibited only minimal dose dependence. In addition, the unbound concentration ratio of stomach to plasma (2.8) at steady state was markedly higher than unity. Taken together, these results suggest that carrier-mediated concentrative uptake processes play an important role in the distribution of acotiamide to the stomach but not skeletal muscle. Topics: Animals; Benzamides; Chromatography, Liquid; Dyspepsia; Gastric Mucosa; Gastrointestinal Agents; Male; Muscle, Skeletal; Protein Binding; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Thiazoles; Tissue Distribution | 2011 |
Z-338. Zeria/Yamanouchi.
Zeria and Yamanouchi are co-developing Z-338, a thiazole-4-carboxamide derivative with prokinetic activities, as a potential treatment for dyspepsia and gastric motility disorders. This compound is currently in phase II clinical trials. Topics: Animals; Benzamides; Biological Availability; Cholinesterase Inhibitors; Clinical Trials, Phase II as Topic; Dogs; Drug Administration Routes; Drug Evaluation, Preclinical; Drug Industry; Drugs, Investigational; Dyspepsia; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Guinea Pigs; Humans; Hypnotics and Sedatives; Molecular Structure; Multicenter Studies as Topic; Rats; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Sweden; Thiazoles; Xenopus | 2004 |