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Background: Irritable bowel syndrome (IBS) has a major negative influence on quality of life, causing cramps, stomach pain, bloating, constipation, etc. Antispasmodics have varying degrees of efficacy. Mebeverine, for example, works by controlling bowel movements and relaxing the muscles of the intestines but has side effects. Therefore, more efficient medication is required. Methods: In the current study, we investigated the synthesis of novel mebeverine analogs and determined ex vivo their spasmolytic and in vitro and ex vivo anti-inflammatory properties. The ability to influence both contractility and inflammation provides a dual-action approach, offering a comprehensive solution for the prevention and treatment of both conditions. Results: The results showed that all the compounds have better spasmolytic activity than mebeverine and good anti-inflammatory potential. Among the tested compounds, 3, 4a, and 4b have been pointed out as the most active in all the studies conducted. To understand their mechanism of activity, molecular docking simulation was investigated. The docking analysis explained the biological activities with their calculated Gibbs energies and possibilities for binding both centers of albumin. Moreover, the calculations showed that molecules can bind also the two muscarinic receptors and interleukin-β, hence these structures would exert a positive therapeutic effect owed to interaction with these specific receptors/cytokine. Conclusions: Three of the tested compounds have emerged as the most active and effective in all the studies conducted. Future in vivo and preclinical experiments will contribute to the establishment of these novel mebeverine derivatives as potential drug candidates against inflammatory diseases in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by abdominal pain or discomfort. Mebeverine is an antispasmodic that has been widely used in clinical practice to relieve the symptoms of IBS. However, its systemic use usually leads to side effects. Therefore, the current paper aimed to synthesize more effective medicines for IBS treatment. We used ring opening of isatoic anhydride for the synthesis in reaction with 2-phenylethylamine. In silico simulation predicted spasmolytic activity for 2-amino-N-phenethylbenzamides. The newly synthesized compounds demonstrated a relaxation effect similar to mebeverine but did not affect the serotonin or Ca2+-dependent signaling pathway of contractile activity (CA) in contrast. Having in mind the anti-inflammatory potential of antispasmodics, the synthesized molecules were tested in vitro and ex vivo for their anti-inflammatory effects. Four of the newly synthesized compounds demonstrated very good activity by preventing albumin denaturation compared to anti-inflammatory drugs/agents well-established in medicinal practice. The newly synthesized compounds also inhibited the expression of interleukin-1β and stimulated the expression of neuronal nitric oxide synthase (nNOS), and, consequently, nitric oxide (NO) synthesis by neurons of the myenteric plexus. This characterizes the newly synthesized compounds as biologically active relaxants, offering a cleaner and more precise application in pharmacological practice, thereby enhancing their potential therapeutic value. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) has a major negative influence on quality of life, causing cramps, stomach pain, bloating, constipation, etc. Antispasmodics have varying degrees of efficacy. Mebeverine, for example, works by controlling bowel movements and relaxing the muscles of the intestines but has side effects. Therefore, more efficient medication is required. Methods: In the current study, we investigated the synthesis of novel mebeverine analogs and determined ex vivo their spasmolytic and in vitro and ex vivo anti-inflammatory properties. The ability to influence both contractility and inflammation provides a dual-action approach, offering a comprehensive solution for the prevention and treatment of both conditions. Results: The results showed that all the compounds have better spasmolytic activity than mebeverine and good anti-inflammatory potential. Among the tested compounds, 3, 4a, and 4b have been pointed out as the most active in all the studies conducted. To understand their mechanism of activity, molecular docking simulation was investigated. The docking analysis explained the biological activities with their calculated Gibbs energies and possibilities for binding both centers of albumin. Moreover, the calculations showed that molecules can bind also the two muscarinic receptors and interleukin-β, hence these structures would exert a positive therapeutic effect owed to interaction with these specific receptors/cytokine. Conclusions: Three of the tested compounds have emerged as the most active and effective in all the studies conducted. Future in vivo and preclinical experiments will contribute to the establishment of these novel mebeverine derivatives as potential drug candidates against inflammatory diseases in the gastrointestinal tract.

Acute gastrointestinal cramping pain (GICP) is a debilitating condition that affects many people worldwide, significantly reducing their quality of life. As such, prompt treatment is crucial. This article will explore relevant literature from databases such as PubMed, Scopus, Google Scholar, Cochrane Library, and Web of Science. Additionally, we searched ClinicalTrials.gov and the WHO ICTRP database for the latest clinical trials. Consensus dictates that antispasmodics such as hyoscine-N-butyl bromide and mebeverine should be the primary treatment for GICP. If these prove ineffective, patients can switch to an antispasmodic with a different mode of action or add acetaminophen/NSAIDs for more severe cases. Currently, several antispasmodics are undergoing clinical trials, including drotaverine, alverine, pinaverium, otilonium bromide, fenoverine, tiropramide, otilonium bromide, trimebutine, and peppermint oil. Well-designed head-to-head studies are necessary to evaluate current antispasmodics' safety, efficacy, pharmacokinetic, and pharmacoeconomics profiles. Recent studies have shown that fixed-dose combinations of antispasmodics + NSAIDs or two different antispasmodics can improve patient compliance and synergistically reduce GICP. Therefore, it is recommended that the global availability and accessibility of these products be enhanced. [ABSTRACT FROM AUTHOR]

Background. Irritable bowel syndrome (IBS) is one of the most common functional disorders of the gastrointestinal tract. According to Russian guidelines, a standard examination using laboratory and instrumental evaluation methods, including colonoscopy, should be performed to establish the diagnosis of IBS. Aim. To characterize the Russian population of IBS patients. Materials and methods. A multicenter observational prospective study ROMERUS was conducted at 35 clinical centers in the Russian Federation. The study included male and female patients aged 18 to 50 with a diagnosis of IBS based on the Rome IV criteria, with no signs of structural gastrointestinal disease. The follow-up duration was 6 months and included three patients' visits to the study site. During the study, data were collected on patients' demographic and clinical characteristics, medical history, and drug therapy. The secondary parameters included the assessment of the proportion of patients with a diagnosis of IBS confirmed by a standard examination among all patients meeting the Rome IV criteria, the evaluation of the change over time of the IBS symptoms, quality of life (QoL), and adherence to therapy. Characterization of the population was performed using descriptive statistics methods. The standard examination results were presented as the percentage of patients with IBS confirmed by the standard examination among all patients meeting the Rome IV criteria, with a two-sided 95% confidence interval. Results. The study included 1004 patients with a diagnosis of IBS according to the Rome IV criteria, with 790 (78.7%) patients included in the final analysis. The mean age of patients was 34.07.5 years; they were predominantly female (70.4%), Caucasian (99.4%), married (55.1%), urban residents (97.5%) with higher education (64.5%) and a permanent position (74.9%). Patients enrolled in the study have low physical activity and lack a healthy diet. The smoking rate was 26.3%. IBS symptoms with predominant constipation (IBS-C) were observed in 28.1% of patients; 28.9% had IBS with predominant diarrhea (IBS-D), 11.9% had mixed-type IBS, and 31.1% had non-classified IBS. The main IBS symptoms were pain (99.7%), abdominal distension (71.1%), and fullness (36.8%). Biliary tract dysfunction (18.9%) and gastritis (17.2%) were the most frequently reported comorbidities. Prior to enrollment, 28% of patients received drug therapy. The most commonly prescribed drug during the study was mebeverine (54.1%). At 6 months of follow-up, there was a significant reduction of abdominal pain, bloating, and distention, and a twofold reduction in the incidence of constipation and diarrhea in the subgroups of patients with IBS-C and IBS-D, respectively. The overall QoL score measured by the IBS-QoL questionnaire increased from 83.0 to 95.2 points (p0.05) during the study. In the overall assessment of their condition, 69.6% of patients noted no symptoms and 25.3% reported marked improvement, 35% were asymptomatic according to the physician's overall assessment of the patient's condition, and 51.8% showed significant improvement. Conclusion. IBS patients in the Russian Federation were characterized. The diagnosis of IBS, established following the Rome IV criteria, is confirmed by the results of a standard examination in 96.3% of patients. The Rome IV criteria for the IBS diagnosis make it possible to establish a diagnosis with a probability of 94.7%. For 6 months of follow-up, there was a clinical improvement with a decrease in the severity of symptoms and a QoL improvement.

The aim of this study was to develop a simple, specific, sensitive and precise LC-MS method for the determination of mebeverine enantiomers in pharmaceutical formulations and it was validated as per ICH guidelines. The chromatographic separation was achieved on Phenomenex® Lux Cellulose 1 (250 mm x 4.6 mm i.d, 5μm particle size) column using mobile phase system containing acetonitrile: 10 mM ammonium acetate (85:15) at the flow rate of 0.8 mL/min. In the spectral investigation by LC-MS, the standard solution of Mebeverine showed major peak at m/z of 430.70, which was assigned to the [M+H] ion of Mebeverine. The described method was linear over the range of 15–75 ng /mL for (±) Mebeverine enantiomers with a correlation coefficient (r2 = 0.999). Detection limits and quantification limits of (+) Mebeverine and (-) Mebeverine were found to be 5 ng/mL and 15 ng/mL respectively. The recovery study of mebeverine from tablet formulation was found to be 99.16%. Mebeverine standard solution and mobile phase were found to be stable for at least 48h. The Mebeverine enantiomers were well resolved with mean retention times of about 1.16 min and 1.20 min respectively. The developed method was extensively validated and proved to be robust, accurate, precise, and suitable for analysis of Mebeverine enantiomers in tablet dosage form. [ABSTRACT FROM AUTHOR]

Among functional gastrointestinal disorders, Irritable bowel syndrome (IBS) rightfully continues to maintain its leading position. IBS is a kind of standard for understanding the pathogenetic essence of functional diseases of the digestive system, since it is the most common, studied and studied pathology. So, for the query "Irritable Bowel Syndrome" in the electronic database PubMed as of July 30, 2022, 16 599 sources were found, and for the query "Irritable Bowel Syndrome" in the scientific electronic library eLIBRARY.RU 6316. The first part of the review deals with topical aspects of the etiology, pathogenesis and clinical presentation of IBS. The urgency of the problem of IBS is associated with a significant decrease in the quality of life of patients. The review focuses on the role of psycho-emotional disorders, changes localized at the level of the intestinal wall; and a new coronavirus infection COVID-19 in the development of IBS. Abdominal pain as the leading manifestation of IBS is associated primarily with spasm. In this context, antispasmodic drugs can be considered not only as symptomatic agents, but also as pathogenetic therapy for IBS. In the second part of the review, the possibilities of one of the myotropic antispasmodics, mebeverine hydrochloride, in the treatment of IBS are considered in detail.

In the structure of gastrointestinal diseases, the pathology of the hepatobiliary system currently ranks second in frequency of occurrence. The stages of diseases of the biliary system can be combined into the so-called “biliary continuum”, when one patient has a consistent development of pathogenetically related diseases of the biliary tract. The progressive course of functional motility disorders of the biliary tract gradually leads to the development of organic pathology, including chronic cholecystitis, the subsequent development of gallstone disease and possible postcholecystectomy complications. Among the diseases of the biliary system, one of the most frequently used diagnoses is chronic cholecystitis. The development of chronic cholecystitis is associated with repeated attacks of acute inflammation or prolonged irritation of large gallstones. The clinical aspects of chronic cholecystitis and other pathologies included in the the «biliary continuum» largely depends on concomitant dyskinesia. There are several directions for the treatment of pathologies of the biliary system: diet therapy, medication, endoscopic and surgical treatment. According to the latest guidelines, the most important direction in modern therapy of diseases of the biliary system is the restoration of the motility of the biliary tract and the normalization of the physicochemical properties of bile. The central place in the treatment of diseases of the “biliary continuum” is given to antispasmodic drugs. The administration of antispasmodics is recommended in order to relieve biliary pain and dyspeptic symptoms caused by spasm of smooth muscles, as well as to control the inflammatory process due to a decrease in the release of pro-inflammatory substances. This article describes in detail the importance of the recovery of the biliary tract motor activity and the improvement of the physico-chemical properties of bile acids.

Introduction. IBS is a functional bowel disorder that has a significant impact on patients and society, especially in terms of quality of life and medical costs.Pathogenesis. It is believed that the pathogenesis of IBS consists of several mechanisms: the syndrome of intersection of functional disorders (gut-brain), stress, visceral hypersensitivity and changes in motor skills.Visceral hypersensitivity. Changes in visceral sensitivity in IBS are characterized by central abnormalities in areas of the cerebral cortex. Motility impairment in IBS manifests itself as abnormal myoelectric activity in the colon, resulting in repetitive contractions of the small intestine and colon, which appear to cause pain.Intestinal microflora. FODMAPs are found in high amounts in some fruits, artificial sweeteners, legumes, and green vegetables and are poorly absorbed by all people. FODMAPs have enzymatic and osmotic effects that may contribute to the onset of symptoms in some patients.The principles of IBS therapy. Treatment for IBS should be based on the type and severity of symptoms. For the treatment of IBS, drugs of various pharmacological groups are used, depending on the prevailing symptoms. These include opioid receptor agonists, bile acid sequestrants, guanylate cyclase agonists, chlorine channel activators, as well as antibiotics, probiotics, antidepressants, 5-HT3 receptor antagonists, and antispasmodics.Myotropic antispasmodics. Drugs with antispasmodic activity are used to treat functional and organic diseases of the gastrointestinal tract as a basic therapy or «on demand». Mebeverine quickly and effectively relieves spasm, pain and the entire complex of intestinal symptoms, in addition, the drug reduces visceral hypersensitivity due to a local anesthetic effect. The drug has a high safety profile and has a number of advantages over drugs of the same pharmacological group.Conclusion. Myotropic antispasmodics have been shown to be highly effective in the treatment of IBS. Mebeverine occupies a special place among myotropic antispasmodics. Its combined action provides a pronounced antispasmodic activity along with a high safety profile.

Introduction: Lower urinary tract symptoms (LUTS) are common in patients suffering from irritable bowel syndrome (IBS). LUTS are categorized into storage, voiding and postmicturition symptoms. Mebeverine, a voltage-gated sodium channel blocker, can alleviate IBS symptoms via inducing smooth muscle relaxation. The effect of mebeverine on LUTS is not cleared yet. Consequently, we aimed to evaluate the effect of mebeverine on LUTS in IBS patients. Materials and Methods: Seventy-five IBS patients were included in the present study. IBS was diagnosed according to the Rome IV criteria. International prostate symptom score (I-PSS) questionnaire was used to evaluate LUTS and quality of life in IBS patient. Patients were treated with 200 mg mebeverine per day. All patients were assessed once before the treatment and then one, three and six months after the treatment with mebeverine. Results: The prevalence and severity of voiding symptoms were significantly higher in males than females (P < 0.05). One-month treatment with mebeverine reduced storage and voiding urinary symptoms in IBS patients (P < 0.01 and P < 0.0001, respectively). The beneficial effects of mebeverine increased over the time and the maximum effect were found following six-months treatment (P < 0.0001). Furthermore, using mebeverine in IBS patients improved the quality of life both in men and women (P < 0.0001). Conclusion: Mebeverine could obviously ameliorate both gastrointestinal and urinary symptoms in IBS patients. These findings may propose that smooth muscle relaxants including mebeverine might be proper therapeutic agents for IBS patients with LUTS. [ABSTRACT FROM AUTHOR]

The present work aims to present two new concepts concerned with chiral separation. First, chiral separation of some enantiomeric drugs, using micelle-based liquid chromatography without any chiral selector, whether in the stationary phase or the mobile phase, was performed. The surfactants used were anionic; sodium dodecyl sulphate, and cationic; cetrimide. The studied analytes include phenyl-ephrine hydrochloride (PHR), cetirizine dihydrochloride (CTZ), and mebeverine hydrochloride (MBV). Successful separation of the enantiomers was attained, giving promising results that may cause a revolution in chiral separation, predicting the possibility of simply prepared aqueous micellar mobile phases of carrying chiral selector ability. The second motive of this work is studying the compatibility of hybrid micelle liquid mobile phases with chiral columns separating CTZ, using cellulose 1 chiral column as a model example. This study may be an environmentally safe substitute for the normal phase mode of elution that is usually applied for chiral separation consuming large amounts of hazardous organic solvents.

Background: Drotaverine and Mebeverine are used for alleviating the pain of IBS, but the evidence for their efficacy is scarce. In this randomised control study, we evaluated and compared their efficacy in improving severity, frequency of pain and its associated symptoms. Methods: Patients fulfilling the ROME III criteria of IBS were evaluated in this randomised control trial during 4 weeks of treatment. Group A (n = 100) received 80 mg Drotaverine and Group B (n = 100) received 135 mg Mebeverine three times a day, 1 hour before meals. Primary outcome measure was, the reduction in severity of pain (>30% reduction) assessed by VAS (0 to 10 scale) & PSS (patient symptoms scores). Results: The pain severity score fell from 6.02 to 4.8 on day 3 in Group A as compared to decrease from 6.72 to 6.62 in Group B (p < 0.01). This significant reduction in pain severity was observed till the end of the study, reducing from 6.02 to 1.78 (74% reduction) in Group A compared to 6.72 to 3.62 (46.1% reduction) in Group B (p < 0.05). There was a significant reduction in pain frequency, straining on stool, a change in one score in Bristol stool chart (BSC), achievement of complete spontaneous smooth bowel movement in Group A, compared to Group B patients. A significant improvement in Patient's evaluation of Global Assessment of Symptoms (p < 0.05) and Patient Assessment of Constipation – Quality Of Life (PAC-QOL) (p < 0.01) was observed in Group A compared to Group B. Conclusion: Drotaverine was significantly superior in efficacy as compared to Mebeverine in alleviating pain severity (starting from day 3), frequency and stools-elated symptoms of IBS.

Objectives: To investigate the efficacy of mebeverine for nocturnal incontinence in male patients with an ileal orthotopic bladder substitute (OBS). Patients and Methods: A randomised controlled trial was carried out for adult male patients who were nocturnal incontinent. Patients were allocated to receive mebeverine 200 mg or placebo once a day in the evening for 3 months. The primary outcome was to compare the continence status between groups, assessed by the urinary domain of the Bladder Cancer Index (BCI) and pad usage. The secondary outcomes were to assess the safety of mebeverine. Results: There were 55 patients in the placebo group and 58 in mebeverine group who completed the follow‐up. The median (interquartile range) interval between OBS surgery and starting treatment was 9 (4–13) years in the placebo group and 9 (6–13) years in the mebeverine group. The mean (SD) 3‐month urinary domain score of the BCI was 70.8 (5.6) and 86.4 (14.2) in the placebo and mebeverine groups, respectively (P < 0.001). At 3 months, 54 (98.2%) and 26 (44.8%) patients required the use of a night‐time pad in the placebo and mebeverine groups, respectively. Mebeverine reduced the risk of pad use by 53.4% (95% confidence interval 40.1–66.6; P < 0.001). Constipation occurred in one (2.1%) and three (5.8%) patients in the placebo and mebeverine groups, respectively; abdominal distention occurred in two (3.8%) of the patients in the mebeverine group (P = 0.25). Conclusion: Mebeverine decreases night‐time pad use and improves the quality of life in male patients with an ileal OBS and is associated with minimal adverse events. [ABSTRACT FROM AUTHOR]

The article is devoted to the diverticular colon disease, its uncomplicated form, the connection with age. Symptoms allowing to define presence at this form of disease of IBS-like symptoms – pains and infringements of the psycho-emotional status are highlighted. The results of psychometric research and psychiatrist’s consultation of 102 patients are presented. The role of obesity in the genesis of diverticular disease is highlighted. The significance of spasmolytic therapy, in particular mebeverine, is presented.

Physicians tend to prescribe brand-name medicines for treating specific diseases. This might be due to the better clinical effects of these medicines compared to the generic ones. The aim of the present study was to evaluate in vitro bioequivalency between five generic products (T1, T2, T3, T4, T5) of mebeverine 200 mg extended-release capsules marketed in Iran and the innovator brand (Colofac® retard, Abbott Healthcare SAS, France). To evaluate the differences between generic products and the innovator brand, weight variation and dissolution analysis were performed. Acceptance value was calculated to investigate weight variation between different products. Dissimilarity factor (f1) and similarity factor (f2) were calculated to differentiate between the dissolution profile of the innovator brand and generic products. Innovator brand and all the generic formulations passed the United States Pharmacopoeia (USP) weight variation test. However, dissolution results indicated that among five generic formulations only T1, T4 and T5 were similar to the innovator brand but T2 and T3 did not pass USP requirements. Some pharmaceutical formulations may pass the pharmacopeia requirements but might show significant differences through in vitro equivalence studies. These differences could result in clinically diverse effects. Moreover, dissolution analysis seems to be a suitable procedure to detect these variations. [ABSTRACT FROM AUTHOR]

Background: Drotaverine and Mebeverine are used for alleviating the pain of IBS, but the evidence for their efficacy is scarce. In this randomised control study, we evaluated and compared their efficacy in improving severity, frequency of pain and its associated symptoms. Methods: Patients fulfilling the ROME III criteria of IBS were evaluated in this randomised control trial during 4 weeks of treatment. Group A (n = 100) received 80 mg Drotaverine and Group B (n = 100) received 135 mg Mebeverine three times a day, 1 hour before meals. Primary outcome measure was, the reduction in severity of pain (>30% reduction) assessed by VAS (0 to 10 scale) & PSS (patient symptoms scores). Results: The pain severity score fell from 6.02 to 4.8 on day 3 in Group A as compared to decrease from 6.72 to 6.62 in Group B (p < 0.01). This significant reduction in pain severity was observed till the end of the study, reducing from 6.02 to 1.78 (74% reduction) in Group A compared to 6.72 to 3.62 (46.1% reduction) in Group B (p < 0.05). There was a significant reduction in pain frequency, straining on stool, a change in one score in Bristol stool chart (BSC), achievement of complete spontaneous smooth bowel movement in Group A, compared to Group B patients. A significant improvement in Patient's evaluation of Global Assessment of Symptoms (p < 0.05) and Patient Assessment of Constipation – Quality Of Life (PAC-QOL) (p < 0.01) was observed in Group A compared to Group B. Conclusion: Drotaverine was significantly superior in efficacy as compared to Mebeverine in alleviating pain severity (starting from day 3), frequency and stools-elated symptoms of IBS. [ABSTRACT FROM AUTHOR]

Background and Aims: Irritable bowel syndrome (IBS) is a chronic relapsing disorder characterized by abdominal pain-discomfort and altered bowel habits. The IBS-diarrhoea predominant subtype (IBS-D) is defined as >25% of bowel movements representing type 6 or 7 of the Bristol Stool Form Scale. Management of IBS-D is mainly symptomatic, including lifestyle modification. Due to absence of standard treatment, multiple drugs are used. A controlled release (CR) form of mebeverine, recommended for spasmodic gastrointestinal disorders (including IBS) has recently been introduced in Indian market. We have conducted a placebo-controlled double blind randomized controlled trial [CTRI/2018/03/012897] to evaluate the effectiveness and safety of this product. Methods: 40 patients of IBS-D were recruited from medicine out-patient department (OPD) of a tertiary care hospital and randomized to two parallel groups. One received mebeverine 200 mg CR tablets twice daily for 8 weeks, while other received matching placebo. Outcome parameters were number of bowel movements per day over past 7 days (NoBM7d), severity of abdominal cramps and IBS quality of life (IBSQoL) score. Medication adherence record and treatment emergent adverse events were captured. Results: Mebeverine group showed modest but statistically significant improvement in NoBM7d, cramps and IBSQoL from baseline to 4 and 8 weeks. The changes within the placebo group were not statistically significant. Also, the intergroup differences at both 4 and 8 weeks were not statistically significant. Adherence was better in mebeverine group and both interventions were well tolerated. Conclusions: Mebeverine 200 mg CR twice daily has modest effect in IBS-D and therefore will not be a good choice for patients with severe symptoms.

The article presents international materials on studying the issue of biliary sludge (BS). The authors also share their own data resulting from conducted studies, where the first group included 1107 patients with BS; the second – 208 patients with different forms of BS; the third group – 40 patients with regular course of BS, in the absence of pharmacological influence; the fourth group – 60 patients (20 patients for each type of BS) with UDCA Exhol 500 mg No. 50 and antispasmodic agent Sparex 200 mg No 30. Intake of Exhol at an initial dose of 15 mg/kg/day was effective in 97% of cases and BS elimination was achieved in 12 weeks. The BS elimination rate depended on its type (1st – 4 weeks, 2–3rd types – 8–12 weeks).

Aim: to assess the effectiveness of mebeverine 200 mg BID in patients with post-cholecystectomy gastrointestinal spasm not requiring surgical treatment. Materials and methods. 218 patients were included in 16 clinical centers in 14 cities in Russia. All patients had post-cholecystectomy gastrointestinal spasms, not requiring surgical treatment and received mebeverine (Duspatalin®) 200 mg BID. The observational assessment period lasted from the moment of their inclusion into the study up to 6 weeks post inlusion. The therapy results were evaluated using visual analog scales (GPA and 11-point numeric rating scale) by patient self-assessment of the dynamics of spasm/discomfort and other post-cholecystectomic gastrointestinal symptoms after 2 and 6 weeks of treatment. Gastrointestinal Quality of Life Index (GIQLI) was used to assess patient quality of life. Results and discussion. All 218 patients completed the 2-week mebeverine treatment course, 101 of them finished the 6-week course (“prolonged population”). Significant positive changes in the relief of abdominal pain and dyspepsia were noted as well as normalization of stool frequency and consistency. A more marked change in values was observed during prolonged (up to 6 weeks) therapy. Both 2-week and 6-week mebeverine courses led to a normalization of patient quality of life. After 6 week therapy, an effect of mebeverine on the quality of life 91% of patients was observed comparable to cholecystectomy itself, speficially related to the quality of life subscore ‘symptoms’. Conclusion. The results of our study demonstrate that mebeverine (Duspatalin®) therapy leads to an effective elimination of clinical symptoms associated with post-cholecystectomy GI-spasm disorders, like abdominal pain, symptoms of dyspepsia and stooldisorders. A more marked change in values was observed during prolonged (up to 6 weeks) therapy.

The present work aims to present two new concepts concerned with chiral separation. First, chiral separation of some enantiomeric drugs, using micelle-based liquid chromatography without any chiral selector, whether in the stationary phase or the mobile phase, was performed. The surfactants used were anionic; sodium dodecyl sulphate, and cationic; cetrimide. The studied analytes include phenyl-ephrine hydrochloride (PHR), cetirizine dihydrochloride (CTZ), and mebeverine hydrochloride (MBV). Successful separation of the enantiomers was attained, giving promising results that may cause a revolution in chiral separation, predicting the possibility of simply prepared aqueous micellar mobile phases of carrying chiral selector ability. The second motive of this work is studying the compatibility of hybrid micelle liquid mobile phases with chiral columns separating CTZ, using cellulose 1 chiral column as a model example. This study may be an environmentally safe substitute for the normal phase mode of elution that is usually applied for chiral separation consuming large amounts of hazardous organic solvents. [ABSTRACT FROM AUTHOR]

Objective: Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract that causes abdominal pain or discomfort and alters bowel with no organic abnormalities. Treatment options for IBS have increased in number in the past decade, and clinicians should not be limited to use only conventional treatments to cure it. This article is a placebo-controlled clinical trial to assess the therapeutic effects of low-dose bismuth subcitrate on symptoms and the health-related quality of life in adult patients with IBS. Methods: This clinical trial was done during July 2015 to January 2016 in Isfahan, Iran. For each of three subtypes (IBS-constipation dominant, IBS-diarrhea dominant [IBS-D], and IBS-mixed), we included patients with IBS aged 18–70 years, diagnosed according to the Rome III criteria. In this study, 129 eligible patients were enrolled, of which 119 continued on the protocol to the end of study. They were allocated in placebo group (Group A) and intervention group (Group B). The medication for Group B was mebeverine and bismuth subcitrate and for Group A was mebeverine and placebo of bismuth subcitrate. Initially, the patients of both groups completed IBS-related questionnaires (IBS-quality of life, IBS-severity scoring system), then given drugs for a 4-week period (1st on-drug period). Then, both groups were given only mebeverine hydrochloride 200 mg capsule for another 4 weeks (off-drug period). At last, Group A and Group B were given medication (2nd on-drug period), the same as 1st on-drug period. Findings: With respect to quality of life, the trend of IBS-QOL score changed significantly during the study period in both the intervention and placebo groups; however, no significant differences were observed between the two groups (P < 0.005). In subgroups analysis, quality of life significantly improved in IBS-D during the study from the first measurement to the end of study (P = 0.004). The trends of changes in the severity of pain during the study between the intervention and control group were significantly different (P = 0.018). Conclusion: According to our study, IBS-D patients' symptoms improved significantly with bismuth therapy. We found that adding low-dose bismuth to mebeverine in nonresponsive IBS patients in conventional treatment could be helpful.

Pharmacokinetic study of prolonged release capsules of mebeverine was carried out on 24 volunteers. It is known that the drug substance is completely metabolized due to first-pass effect. Therefore, pharmacokinetic parameters of the main metabolites -mebeverine acid and desmethyl mebeverine acid were measured. Bioanalytical method was developed to measurement of concentrations of these metabolites in blood plasma by using HPLC-MS/MS.

Background and Aims: Irritable bowel syndrome (IBS) is a chronic relapsing disorder characterized by abdominal pain-discomfort and altered bowel habits. The IBS-diarrhoea predominant subtype (IBS-D) is defined as >25% of bowel movements representing type 6 or 7 of the Bristol Stool Form Scale. Management of IBS-D is mainly symptomatic, including lifestyle modification. Due to absence of standard treatment, multiple drugs are used. A controlled release (CR) form of mebeverine, recommended for spasmodic gastrointestinal disorders (including IBS) has recently been introduced in Indian market. We have conducted a placebo-controlled double blind randomized controlled trial [CTRI/2018/03/012897] to evaluate the effectiveness and safety of this product. Methods: 40 patients of IBS-D were recruited from medicine out-patient department (OPD) of a tertiary care hospital and randomized to two parallel groups. One received mebeverine 200 mg CR tablets twice daily for 8 weeks, while other received matching placebo. Outcome parameters were number of bowel movements per day over past 7 days (NoBM7d), severity of abdominal cramps and IBS quality of life (IBSQoL) score. Medication adherence record and treatment emergent adverse events were captured. Results: Mebeverine group showed modest but statistically significant improvement in NoBM7d, cramps and IBSQoL from baseline to 4 and 8 weeks. The changes within the placebo group were not statistically significant. Also, the intergroup differences at both 4 and 8 weeks were not statistically significant. Adherence was better in mebeverine group and both interventions were well tolerated. Conclusions: Mebeverine 200 mg CR twice daily has modest effect in IBS-D and therefore will not be a good choice for patients with severe symptoms. [ABSTRACT FROM AUTHOR]

Mebeverine is a musculotropic antispasmodic drug that is widely used in the treatment of irritable bowel syndrome. As an ester of mebeverine alcohol and veratric acid, mebeverin is quickly metabolized and is practically undetectable in blood plasma. The main goal of this work was establishing the structure of the main metabolites of mebeverin in human blood plasma. The study was conducted by time-of-flight mass spectrometry (LC-IT-TOF MS), metabolites of mebeverine were extracted from plasma with acetonitrile. When comparing chromatograms of blood plasma obtained before and after drug administration, four main peaks of metabolites were detected. To establish the structure of the compounds, mass spectra of the first and second order were taken. The first-order spectra were used to calculate the metabolite formula and the structure was determined from the fragmentation spectra, as well as by comparing the fragmentation spectra of mebeverine and its proposed metabolites. The proposed compounds were synthesized, and their structure was confirmed using NMR and chromatography-mass spectrometry. Four main metabolites were found in this study: desmethylmebeverine acid (DMAC), glucuronide product of DMAC (DMAC-Glu), mebeverine acid (MAC) and mebeverine alcohol (MAL). The results complement the available literature data about the veratric acid metabolism, urine, and microsomal studies. According to the data obtained, the main metabolite of mebeverine in the blood is DMAC. The concentration of MAC after mebeverine administration is almost ten times less than DMAC, the content of MAL and DMAC-Glu is insignificant, and probably does not affect the pharmacological effect of mebeverine. Therefore, the concentration of DMAC is the main parameter to be monitored in pharmacokinetics studies. [ABSTRACT FROM AUTHOR]

A sensitive, selective and precise high-performance thin-layer chromatographic method was developed and validated for the simultaneous determination of alprazolam and mebeverine, both as bulk drugs and in formulations. The method employed HPTLC aluminium plates that had been pre-coated with silica gel 60F-254 as the stationary phase, while the solvent system was acetone:methanol:acetic acid (6:4:0.1, v/v/v). The Rf values of alprazolam and mebeverine were observed to be 0.80 ± 0.08 and 0.60 ± 0.05, respectively. The densitometric analysis was carried out in absorbance mode at 225 nm. The linear regression analysis for the calibration plots showed a good linear relationship for alprazolam and mebeverine over concentration ranges of 600 to 3600 ng/spot and 1000 to 6000 ng/spot, respectively. The limit of detection and the limit of quantification for alprazolam (mebeverine) were determined to be 63.97 (11.35) ng/spot and 193.85 (34.40) ng/spot, respectively. Alprazolam and mebeverine stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation, dry heat degradation and photo-degradation. Both drugs were found to be susceptible to acid and alkali hydrolysis, chemical oxidation and photo-degradation, whereas both were found to be stable towards dry heat. The degraded product peaks were well resolved from the pure drug peak and displayed a significant difference in their Rf values. Stressed samples were assayed using the developed HPTLC method. The proposed method was validated with respect to linearity, accuracy, precision and robustness. The method was successfully applied to the estimation of alprazolam and mebeverine in marketed formulations. Statistical analysis showed that the method is repeatable, selective, and precise.

Background: Selective norepinephrine-serotonin receptor inhibitors (SNRIs) such as duloxetine have already shown beneficial effects on symptoms in irritable bowel syndrome (IBS) patients. The purpose of the present investigation was to assess the efficacy of duloxetine in the symptom and quality of life improvement in diarrhea predominant-IBS (IBS-D) patients. Materials and Methods: IN a randomized, double-blind and placebo-controlled study, sixty patients diagnosed with IBS-D (ROM-IV criteria), referred to the gastrointestinal clinic of Rasoul-e-Akram Hospital of Iran university of medical sciences, randomly assigned in the treatment groups, group A: patients who received 135 mg mebeverine tablet twice a day combined with 30 mg duloxetine capsule per day and group B, who received the same regimen, except for placebo capsule once per day instead of duloxetine for twelve weeks. The assessment was performed using the IBS severity index, and IBS quality of life questionnaire (IBS-QOF) at baseline, and weeks 4, 8, and 12 after beginning the treatment. Drug adverse effects and compliance to treatment were evaluated every 2 weeks after starting the treatment. Results: Sixty patients completed the trial. The duloxetine group showed significantly greater improvement on the IBS symptoms (P < 0.001), and the IBS-QOF (P < 0.001) in comparison to the placebo group at the endpoint. Conclusions: This study showed that adding duloxetine to mebeverine is safe with good efficacy on symptoms and QOL improvement in IBS-D patients. Besides, this study showed that 12 weeks' treatment duration is significantly more effective than 4 weeks' treatment, and drug adverse effects are more prominently seen in the first 2 weeks of treatment.

A new liquid chromatographic method with stability-indicating potential was developed and validated for estimation of mebeverine hydrochloride in formulations using lacidipine as internal standard. A contemporary approach of analytical life-cycle management was followed to develop a robust and reliable chromatographic method. Scouted method variables such as % acetonitrile, flow rate and pH were optimized using design of experiment approach and their effect on critical quality attributes was studied. The attributes viz. resolution and theoretical plates of mebeverine, were highly influenced by % acetonitrile and flow rate of mobile phase. Chromatographic method specificity was ensured by degrading the drug forcefully. Validation studies postulated method acceptability and suitability for estimating mebeverine in both bulk as well as tablet formulation. Results for parameters viz. linearity (0.5-150 µg/mL), accuracy (>98%) and precision (<2%) advocated method reliability. Overall the method was reliable and of optimum quality and, possess the potential of application in routine and bio-analytical purposes. [ABSTRACT FROM AUTHOR]

A new simple, rapid and sensitive high pressure liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) method was developed and validated for simultaneous analysis of mebeverine metabolites as: mebeverine alcohol (MAL), mebeverine acid (MAC) and desmethylmebeverine acid (DMAC) in human plasma. Sample preparation was performed by protein precipitation following the separation of analytes using an Acquity UPLC BEN C8 column 1.7 mm 2.1 × 50 mm (Waters, USA). 2 H 5 -desmethylmebeverine acid ( 2 H 5 -DMAC) was used as the internal standard (IS). The proposed method was validated with linear ranges of 0.1–10 ng/mL; 1–100 ng/mL and 5–1000 ng/mL for MAL, MAC and DMAC, respectively. Accuracy for all analytes (%RE), given as deviation between nominal and measured concentration and assay variability (CV) ranged from −4.04% to 4.60% and from 0.31% to 6.43% respectively both for within- and between-run. The overall recoveries for all metabolites were above 85%. The proposed method was used successfully for analysis of real samples from a pharmacokinetics study. [ABSTRACT FROM AUTHOR]