The Effect of Trimebutine and/or Helicobacter pylori Eradication on the Gastroesophageal Reflux Disease, Irritable Bowel Syndrome, and Functional Dyspepsia Overlapping Disorders

No abstract available.

The Effect of Trimebutine on the Overlap Syndrome Model of Guinea Pigs

BACKGROUND/AIMS: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) disorders and these patients frequently overlap. Trimebutine has been known to be effective in controlling FD co-existing diarrhea-dominant IBS, however its effect on overlap syndrome (OS) patients has not been reported. Therefore, we investigated the effect of trimebutine on the model of OS in guinea pigs. METHODS: Male guinea pigs were used to evaluate the effects of trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated for 1 hour. The next treatment of 10 μg/kg of CRF was intraperitoneally injected and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic transits were assessed after the same order and concentrations of trimebutine and CRF treatment by fecal pellet output assay. RESULTS: Different concentrations (1, 3, and 10 μg/kg) of rat/human CRF peptides was tested to establish the OS model in guinea pigs. CRF 10 μg/kg was the most effective dose in the experimental OS model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly reversed the upper and lower GI transit of CRF induced OS model. Trimebutine significantly increased upper GI transit while it reduced fecal pellet output in the CRF induced OS model. CONCLUSIONS: Trimebutine has been demonstrated to be effective on both upper and lower GI motor function in peripheral CRF induced OS model. Therefore, trimebutine might be an effective drug for the treatment of OS between FD and IBS patients.

Effect of antispasmodic agents for the treatment of irritable bowel syndrome

Antispasmodics are effective in reducing abdominal pain and controlling spasm. Irritable bowel syndrome (IBS) patients have characteristic key factors such as intestinal motility disorder and visceral hypersensitivity. So antispasmodics have been used in the treatment of IBS for decades. Mebeverine blocks intestinal peristalsis but are not significantly better than placebo. Alverine citrate combined with simethicone is effective treatment option in IBS. Otilonium and pinaverium bromide are poorly absorbed agents, so they have mostly local effect with minimal systemic adverse events. Phloroglucinol controls acute exacerbation of abdominal pain effectively. Tiropramide reduce abdominal discomfort without serious adverse events. Fenoverine control spasm in spastic colon but does not affect normal contraction. Trimebutine have dual actions that it inhibits hyperactive colon and activates hypomotile colon. Each drug has advantages and disadvantages. Antispasmodics are considered as the first treatment option of pain-dominant IBS.

Efficacy of Fenoverine and Trimebutine in the Management of Irritable Bowel Syndrome: Multicenter Randomized Double-blind Non-inferiority Clinical Study / 대한소화기학회지

BACKGROUND/AIMS: Antispasmodic agents have been used in the management of irritable bowel syndrome. However, systematic reviews have come to different conclusions about the efficacy in irritable bowel syndrome. Fenoverine acts as a synchronizer of smooth muscle in modulating the intracellular influx of calcium. We compared fenoverine with trimebutine for the treatment of patients with IBS. METHODS: A multicenter, randomized, double-blind, non-inferiority clinical study was conducted to compared fenoverine with trimebutine. Subjects were randomized to receive either fenoverine (100 mg three times a day) or trimebutine (150 mg three times a day) for 8 weeks. A total of 197 patients were analyzed by the intention-to-treat approach. The primary endpoint was the proportion of patients who had 30% reduction in abdominal pain or discomfort measured by bowel symptom scale (BSS) score at week 8 compared to the baseline. The secondary endpoints were changes of abdominal bloating, diarrhea, constipation, overall and total scores of BSS, and overall satisfaction. RESULTS: At week 8, fenoverine was shown to be non-inferior to trimebutine (treatment difference, 1.76%; 90% CI, -10.30-13.82; p=0.81); 69.23% (54 of 78 patients) of patients taking fenoverine and 67.47% (56 of 83 patients) of patients taking trimebutine showed 30% reduction in abdominal pain or discomfort compared to the baseline. There results of the secondary endpoints were also comparable between the fenoverine group and the trimebutine group. CONCLUSIONS: Fenoverine is non-inferior to trimebutine for treating IBS in terms of both efficacy and tolerability.

The Incidence of Irritable Bowel Syndrome in Children Using the Rome III Criteria and the Effect of Trimebutine Treatment

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders and when compared to the vast knowledge pertaining to adults with IBS, very little is known about IBS in children and adolescents. We aimed to explore the prevalence of IBS, identify symptoms and contributing factors and also to examine the efficacy of trimebutine maleate in children and adolescents. METHODS: The study involved 345 children and adolescents (4-18 years) and parents were requested to fill in a questionnaire, Rome III criteria was used to diagnose IBS. To exclude organic disease, all patients underwent medical investigations. Half of the randomly selected IBS patients were treated with trimebutine maleate while the rest of IBS patients were not. The IBS patients were reevaluated at the end of 3 weeks. RESULTS: The prevalence of IBS according to Rome III criteria in children and adolescents was 22.6% and IBS with constipation was the predominant subtype. Back pain (OR, 6.68), headache (OR, 4.72) and chronic fatigue (OR, 3.74) were significantly higher in IBS group. The prevalence of IBS in both parents and depression in mothers was greater for the patient group than the healthy controls (P < 0.0001). The prevalence of functional dyspepsia in IBS group was 80.8% and was significantly higher than control group. Clinical recovery was seen in 94.9% of the trimebutine maleate group versus spontaneous recovery in 20.5% of the non-medicated group. The difference was significant (P < 0.0001). CONCLUSIONS: IBS is a common disorder in children and adolescents. IBS is closely associated with somatic and familial factors. Trimebutine maleate is effective for pediatric IBS patients.

Estudio de bioequivalencia entre dos productos: trimebutina de liberación prolongada de laboratorios Leti SAV vs debridat AP® de laboratorios Pfizer, luego de administar una dosis única de 300 mg en voluntarios sanos / Bioequivalence study of two products trimebutine extended release vs debridat SAV Leti laboratories AP Pzizer after administering a single dose of 300 mg in healthy volunteers

El objetivo del estudio fue evaluar la bioequivalencia entre dos formulaciones de liberación prolongada de trimebutina 300 mg, luego de una administración única en voluntarios sanos, a través de la determinación de su metabolito activo la desmetil-trimebutina. Se trata de un estudio abierto, randomizado, balanceado, con control activo, de dosis simple, cruzado, con dos períodos separados por un período de descanso y secuencial, realizado en 12 voluntarios sanos de ambos sexos. Los voluntarios recibieron de acuerdo al esquema asignado por la aleatorización y en dos períodos, una dosis única por vía oral después de un ayuno de 10 horas, de un comprimido de una formulación conteniendo 300 mg de Trimebutina AP de Laboratorios LETI S.A.V., o del producto de referencia DEBRIDAT AP®, de Laboratorios Pfizer. Después de la última muestra de sangre del primer período hubo un tiempo de lavado de siete días, luego del cual los voluntarios que recibieron el producto test en el primer período recibieron el producto de referencia y viceversa. Las tomas de muestras se realizaron antes de la dosis (tiempo cero), 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 24 h y 36 h. El análisis estadístico se realizó utilizando un paquete estadístico del programa Equiv test, empleándose el análisis de la varianza (ANOVA) de los parámetros cinéticos AUC 0-inf, AUC 0-36 h y Cmax y la aplicación de los intervalos de confianza para el 90%. En el análisis comparativo se tomaron los intervalos de confianza con el rango de referencia de 0.8-1.25%. Para la Trimebutina test los valores fueron: Cmax 1343.49 +/- 585.58, AUC 0-36 de 8197.19 +/- 3995.23 y AUC 0-inf de 8198.36 +/- 3995.3. Para la formulación de referencia los valores fueron de: Cmax 1023.99 +/- 587.57, AUC 0-36 7221.15 +/- 3211.97 y AUC 0-inf de 7225.97 +/- 3211.62 sin diferencias significativas entre los grupos...

The objective of this study is to assess the bioequivalence of two sustained release formulations of trimebutine 300 mg, after a single administration in healthy volunteers, through determination of the active metabolite desmethyl-trimebutine. This is an open, randomized, balanced, active controlled, single dose, crossover study with two periods separated by a rest period and sequentially, conducted in 12 healthy volunteers of both sexes. Volunteers were assigned according to the randomization scheme and two periods, a single oral dose after fasting for 10 hours, a tablet formulation containing 300 mg of trimebutine AP LETI SAV Laboratories, or product Reference DEBRIDAT AP®, Pfizer Laboratories. After the last blood sample of the first period there will be a wash time of seven days, after which the volunteers received the test product in the first period will received the reference product and viceversa. The sampling is performed: before dosing (time zero), 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 24 h and 36 h. Statistical analysis was performed using a statistical package Equiv test program, using analysis of variance (ANOVA) of the kinetic parameters AUC 0-inf, AUC 0-36h and Cmax and application of confidence intervals for 90%. In the comparative analysis we used the confidence intervals with the reference range of 0.8-1.25%. For the Trimebutine test values were Cmax 1343.49 +/- 585.58, AUC 0-36 of 8197.19 +/- 3995.23 and AUC 0-inf 8198.36 +/- 3995.3. For the formulation of reference values were: Cmax 1023.99 +/- 587.57, AUC 0-36 7221.15 +/- 3211.97 y AUC 0-inf of 7225.97 +/- 3211.62 no significant differences between groups. This study found that the Cmax and AUC, its log-transformed means and confidence intervals 90% away from each other not less than 80% or over 125%, so that both products are considered bioequivalent and therefore interchangeable

Comparative study on irritable bowel syndrome treated with acupuncture and western medicine / 中国针灸

<p><b>OBJECTIVE</b>To compare the differences in the therapeutic effect on irritable bowel syndrome (IBS) between acupuncture at Tianshu (ST 25) and Dachangshu (BL 25) and western medication with Trimebutine Maleate.</p><p><b>METHODS</b>Forty cases were divided randomly into an acupuncture group and a western medication group, 20 cases in each one. In acupuncture group, acupuncture was applied to Tianshu (ST 25) and Dachangshu (BL 25). Ziwu Daojiu needling technique was adopted, once daily. In western medication group, Trimebutine Maleate capsule was administered, 2 capsules in each time, 3 times per day. The assessment on the therapeutic effect was performed in 4 weeks of treatment in two groups.</p><p><b>RESULTS</b>As compared with those before treatment, the time of abdominal pain, the frequency of abdominal pain, the morbidity of abnormal stool appearance, the morbidity of defecation abnormality, the morbidity of mucus stool and the score of bloating or abdominal pain on bowel movement were all reduced after treatment in two groups (all P < 0.01). The results in acupuncture group were much more significant than those in western medication group (the total score: 16.70 +/- 2.40 vs 15.70 +/- 3.01, P < 0.01). The total effective rate in acupuncture group was 95.0% (19/20), which was superior to that of 70.0% (14/20) in western medication group (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture at Tianshu (ST 25) and Dachangshu (BL 25) may remarkably relieve the clinical symptoms of IBS and its efficacy is superior to that of oral medication with Trimebutine Maleate.</p>

Comparação entre o sumatriptano, a trimebutina, o meloxicam e a associação dos três fármacos no tratamento agudo de enxaqueca / Comparison among sumatriptane, trimebutine, meloxicam and the association of those drugs in the acute treatment of migraine

JUSTIFICATIVA E OBJETIVOS: A crise aguda de migrânea geralmente leva a grande incapacidade econômica e social para aqueles que sofrem deste transtorno. A fisiopatologia é complexa e envolve múltiplos mecanismos centrais e periféricos. O tratamento agudo tem como objetivo aliviar a dor e os fenômenos associados como a náusea e fotofobia, sem causar efeitos adversos importantes. Apesar do desenvolvimento de fármacos específicos como os triptanos, para o tratamento agudo, a sua eficácia ainda é baixa. O objetivo deste estudo foi comparar a eficácia e a tolerância da trimebutina, meloxicam, sumatriptano e a associação dos três fármacos no tratamento das crises agudas de migrânea de moderada a forte intensidade.MÉTODO: Após aprovação pelo Comitê de Ética das Instituições foram incluídos neste estudo prospectivo, duplamente encoberto e aleatório, 50 pacientes, sendo 43 mulheres e 7 homens, com idade entre 18 e 65 anos, portadores de migrânea com ou sem aura, que utilizavam medicação profilática, exceto anti-inflamatórios não esteroides (AINES). Foram tratadas quatro crises de migrânea de moderada a forte intensidade de cada paciente, com 200 mg de trimebutina, 50 mg de sumatriptano, 15 mg de meloxicam ou com a associação de 200 mg de trimebutina, 50 mg de sumatriptano e 15 mg de meloxicam. Os pacientes foram aleatorizados em 4 grupos de acordo com a ordem de chegada, de modo que o primeiro paciente incluído recebeu trimebutina para a primeira crise, sumatriptano para a segunda crise, meloxicam para a terceira crise e a associação entre os 3 fármacos para a quarta crise. O segundo paciente incluído recebeu sumatriptano para a primeira crise, meloxicam para a segunda superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.crise, a associação para a terceira crise e a trimebutina para a quarta crise, e assim sucessivamente. A intensidade da crise de migrânea foi avaliada a partir da ingestão da cápsula com escala categorizada verbal na qual: 0 - sem dor, 1 - cefaleia leve, 2 - cefaleia moderada e 3 - cefaleia intensa. Cada paciente foi orientado para preencher o relatório de crise para cada crise tratada, na qual anotava a intensidade da cefaleia, a presença de náusea, fotofobia e dos efeitos adversos, e o uso da medicação de resgate, 100 mg de indometacina por via retal. RESULTADOS: Completaram o estudo 42 pacientes. Em uma hora 9,5% dos pacientes que utilizaram a associação dos fármacos estavam livres da dor, comparados com 14,2% com a trimebutina e sumatriptano e 2,4% com o meloxicam (p = 0,479). Em duas horas 21,4% dos pacientes que usaram a associação estavam livres da dor, comparados com 11,9% com a trimebutina, 26,1% com sumatriptano e 23,8% com o meloxicam (p = 0,555). Tanto a associação trimebutina, sumatriptano e meloxicam como os fármacos trimebutina, sumatriptano e meloxicam isolados foram efetivos para controlar a náusea e fotofobia após 1 e 2h para náusea (p = 0,157 e 0,587) e fotofobia (p = 0,671 e 0,929, embora sem diferença estatisticamente significativa entre eles. Dez pacientes em uso da associação dos fármacos, 6 em uso da trimebutina, 5 em uso do sumatriptano e 5 em uso do meloxicam relataram efeitos colaterais. CONCLUSÃO: Este estudo demonstrou que a associação sumatriptano, meloxicam e trimebutina não foi superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.

BACKGROUND AND OBJECTIVES: Acute migraine crisis often leads to major economic and social disability for those suffering from such syndrome. Pathophysiology is complex involving several central and peripheral mechanisms. The acute treatment aims at evaluating pain and associated phenomena, such as nausea and photophobia, without causing major adverse effects. Notwithstanding the development of specific drugs for the acute treatment, such as triptanes, their efficacy is still low. This study aimed at comparing efficacy and tolerance of trimebutine, meloxicam, sumatriptane and the association of such drugs to treat moderate to severe acute migraine crises.METHOD: After the Institutions? Ethics Committee approval, participated in this prospective, double-blind and randomized study 50 patients, being 43 females and 7 males, aged between 18 and 65 years, with migraine with or without aura, under prophylactic medication, except non-steroid anti-inflammatory drugs (NSAIDS). Patients were treated for 4 moderate to severe migraine crises with 200 mg trimebutine, 50 mg sumatriptane, 15 mg meloxicam, or with the association of 200 mg trimebutine, 50 mg sumatriptane and 15 mg meloxicam. Patients were randomized in 4 groups according to their arrival, so that the first patient included received trimebutine for the first crisis, sumatriptane for the second crisis, meloxicam for the third crisis and the association of the three drugs for the fourth crisis. The second patient included received sumatriptane for the first crisis, meloxicam for the second crisis, the association for the third crisis and trimebutine for the fourth crisis, and so on and so forth. Migraine crisis intensity was evaluated as from the ingestion of the first tablet with verbal categorized scale where: 0 = no pain, 1 = mild headache, 2 = moderate headache, 3 = severe headache. All patients were oriented to fill a crisis report for each treated crisis, where they would record headache intensity, presence of nausea, photophobia and adverse effects and the use of rescue medication, 100 mg of rectal indometacin.RESULTS: Forty-two patients completed the study. In one hour 9.5% of patients using the association of drugs were free of pain, as compared to 14.2% with trimebutine and sumatriptane and 2.4% with meloxicam (p = 0.479). In two hours 21.4% of patients using the association were free of pain, as compared to 11.9% with trimebutine, 26.1% with sumatriptane and 23.6% with meloxicam (p = 0.555). Both the association of trimebutine, sumatriptane and meloxicam and trimebutine, sumatriptane and meloxicam alone were effective to control nausea and photophobia after 1 and 2 h for nausea (p = 0.157 and 0.587) and photophobia (p = 0.671 and 0.929) although without statistically significant difference among them. Ten patients under the association of drugs, 6 under trimebutine, 5 under sumatriptane and 5 under meloxicam have reported side effects. CONCLUSION: This study has shown that the association of sumatriptane, meloxicam and trimebutine was not better than each of those drugs alone to control pain, nausea and photophobia during moderate to severe migraine crises. In addition, the combination of drugs has shown a higher incidence of adverse effects.

Efectividad de la trimebutina como inductor de la motilidad intestinal durante el post-operatorio de cirugía abdominal de emergencia / Effectiveness of trimebutine as an intestinal motility inductor during abdominal post operative emergency surgery

Evaluar la efectividad de la trimebutina como inductor de la motilidad intestinal durante el período postoperatorio de cirugía abdominal de emergencia, en los pacientes que ingresan al servicio de cirugía general del Hospital Domingo Luciani, durante el período de junio del 2007 a junio del 2008. Estudio de tipo descriptivo, prospectivo y comparativo, con muestreo aleatorio para casos y controles. La muestra esta constituida por 158 pacientes: 79 casos y 79 controles, a quienes se les identificó signos y síntomas de la motilidad intestinal a través del interrogatorio y el examen físico. De las variables estudiadas, sólo la expulsión de flatos a las 24 horas (34,2 por ciento) casos vs el 13,9 por ciento controles); a las 48 horas (78,5 por ciento casos vs 36,7 por ciento controles), la presencia de ruidos hidroaéreos y evacuaciones fue mayor en el grupo de los casos, obteniéndose resultados significativamente estadísticos. El resto de las variables no fue estadísticamente significativo. La trimebutina actúa como un inductor de la motilidad intestinal, acortando el tiempo de duración del íleo postoperatorio de los pacientes a los cuales se le realiza laparotomía exploratoria de emergencia.

Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy subjects / 药学学报

<p><b>AIM</b>To develop an HPLC-ESI-MS assay for determination of trimebutine in human plasma and to investigate the pharmacokinetics and bioequivalence of two trimebutine tablets in human.</p><p><b>METHODS</b>After being made alkaline with saturated sodium bicarbonate, plasma was extracted by cyclohexane and separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (pH 3.5)-methanol (18:82). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 388 for trimebutine and m/z 280 for the internal standard (sibutramine, IS). The fragmentor voltage was 50 V. A randomized cross-over design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer.</p><p><b>RESULTS</b>Calibration curve was linear over the range of 0.3 - 150 microg x L(-1). The main pharmacokinetic parameters of T1/2, Tmax and Cmax were (9.2 +/- 2.8) h, (1.0 +/- 0.3) h and (40 +/- 20) microg x L(-1) for the reference tablet; (9.2 +/- 2.3) h, (0.9 +/- 0.4) h and (41 +/- 20) microg x L(-1) for the test tablet. The relative bioavalability of the test tablet was (97 +/- 13)%. The results of variance analysis and two one-sided t-test showed that there was no significant difference between the two formulations in the AUC and Cmax.</p><p><b>CONCLUSION</b>The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.</p>

A normalizaçäo da motricidade digestiva / Gastrointestinal motility normalization

Descrevem-se, em revisäo rápida, os mecanismos reguladores da motricidade do tubo digestivo, passando-se em seguida a tecer consideraçöes sobre os medicamentos que agem neste terreno. Inicia-se por relembrar os medicamentos mais antigos, carminativos e eupépticos. Em seguida säo revistos os antispasmódicos, anticolinérgicos e antieméticos. Passando-se aos bloqueadores dopaminérgicos, säo revisados sucintamente os ortopramídicos (derivados da benzamida). Finalmente é focalizado o trimebutino, medicaçäo orginal, considerada como verdadeiro normalizador e harmonizador da motricidade digestiva

A Clinical Trial of Polybutine Syrup to Pediatric G-I Symptomes

This clinical trial was undertaken on 32 infants and chhildren who had G-I symptoms caused by a few diseases, such as meningitis, parenteral infection and intestinal infection. Out of 32 patients, six had vomiting only, caused by meingitis and habitual vomiting, eighteen had vomiting and diarrhea both which caused by parenteral infection and rest of them (8) had diarrhea only, caused by intestinal infection. Polybutine syrup, which 5.0 ml contain 24 mg of trimebutine, was given to these patients as follows; 2.5 ml twice a day at 6 months of age, 5.0 ml twice a day at 6 months to one year and 10 ml three times a day at 1-5 years of age. In ten of 24 patients, who had vomiting only (6), vomiting and diarrhea (18), the symptoms were improved within 48 hours, and rest of them (10) was also shown the improvement of their symptoms within 5 days after medication. In comparison of polybutine treated group and not treated group, the effectiveness of polybutine treatment for the symptoms was statistically meaningful.