Eficácia e segurança do Esomeprazol e Lansoprazol comparados ao Omeprazol para o tratamento de doença do refluxo gastroesofágico em adultos: revisão rápida / Effectiveness and safety of esomeprazole and lansoprazole compared to omeprazole for the treatment of gastroesophageal reflux disease in adults: rapid review

Tecnologia: Esomeprazol e lansoprazol. Indicação: Tratamento de doença do refluxo gastroesofágico em adultos. Pergunta: Esomeprazol e lansoprazol são mais eficazes e toleráveis que o omeprazol já incorporado ao SUS para o tratamento de Doença do Refluxo Gastroesofágico (DRGE) em adultos? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas três revisões sistemáticas com meta-análise, que atendiam aos critérios de inclusão. Conclusão: O esomeprazol era mais eficaz para cicatrização da lesão nos casos de esofagite erosiva, prevenção da mucosa do esôfago, maior controle de ácido no tratamento de curto prazo (4 e 8 semanas) de esomeprazol 40mg e tratamento de longo prazo (6 meses) de esomeprazol 20mg. A taxa de resposta no alívio dos sintomas, o esomeprazol 20mg e 40mg apresentou ser mais eficaz, especialmente, na azia e dor epigástrica. Quanto ao perfil de segurança, não houve diferença significativa entre as taxas de eventos adversos, todos medicamentos eram parecidos entre si

Technology: Esomeprazole and Lansoprazole. Indication: Treatment of gastroesophageal reflux disease in adults. Question: Are Esomeprazole and Lansoprazole more effective and tolerable than omeprazole already incorporated into SUS for the treatment of Gastroesophageal Reflux Disease (GERD) in adults? Methods: A rapid review of evidence, an overview of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Three systematic reviews with meta-analysis were selected, which met the inclusion criteria. Conclusion: Esomeprazole was more effective in achieving wound healing in cases of erosive esophagitis, prevention of esophageal mucosa, greater acid control in short-term treatment (4 and 8 weeks) of esomeprazole 40mg and long-term treatment (6 months) of esomeprazole 20mg. the response rate in symptom relief, esomeprazole 20mg and 40mg proved to be more effective, especially in heartburn and epigastric pain. As for the safety profile, there was no significant difference between the rates of adverse events, all drugs were similar to each other

Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Helicobacter pylori Infection: A Nationwide Randomized Trial in Korea

BACKGROUND/AIMS: This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. METHODS: Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. CONCLUSIONS: The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.

Effect of sequential therapy on treatment of Helicobacter pylori infection in children / Efecto de la terapia secuencial en el tratamiento de la infección por Helicobacter pylori en niños

Background: Helicobacter pylori infection which plays a major role in the etiology of chronic gastritis and duodenal ulcers in children and adults is one of the commonest chronic infection worldwide. Cure of the infection leads to healing of gastric inflammation and prevention of peptic ulcer. Objective: The aim of this study was to evaluate the efficacy of the sequential therapy for treatment of Helicobacter pylori infection. Materials and methods: In this study, 40 children with symptoms of H. Pylori that the infection was proved by endoscopy and biopsy and rapid urease test (UBT) were enrolled, and received sequential therapy (Lansoprazol, Amoxicillin) for 5 days and (Lansoprazol, Metronidazole and Clarithromycin) for next 5 days. The eradication rate of therapy was evaluated by stool antigen test 6 weeks after completion of therapy. This study was carried out in Pediatric Gastroenterology Clinic of Shiraz University of Medical Sciences, Shiraz, Iran. This study was approved by ethic committee of Shiraz University of Medical Sciences. Results: Forty children with mean age of (10.8±4 years) were evaluated. The most common symptom on first admission was epigastric pain (82.5%), with mean duration of symptoms (16±14.5 month). The most common endoscopic findings was redness and erosion of the antrum (55%) and the most pathologic findings was chronic gastritis (77.5%). The most drug adverse effect was nausea (22.5%). The eradication rate of sequential therapy was 82.5%. Conclusion: Eradication rate of sequential therapy was 82.5% among our cases.

Antecedentes: La infección por Helicobacter pylori, que juega un rol principal en la etiología de la gastritis crónica y las úlceras duodenales en niños y adultos, es una de las infecciones crónicas más comunes en el mundo. La cura de esta infección lleva a la cura de la inflamación gástrica y a la prevención de la úlcera péptica. Objetivo: Evaluar la eficacia de la terapia secuencial en el tratamiento de la infección por Helicobacter pylori. Material y métodos: En este estudio, se enrolaron 40 niños con síntomas en los que la infección por H. pylori se demostró por endocopía con biopsia y prueba rápida de ureasa (UBT) y recibieron terapia secuencial (Lansoprazol, Amoxicilina) por 5 días y (lansoprazol, metronidazol y clarotromicina) por otros 5 días. La tasa de erradicación de la terapia se evaluó por prueba de antígeno en heces 6 semanas después de terminar la terapia. Este estudio se llevó a cabo en la Clínica de Gastroenterología Pediátrica de la Universidad de Ciencias Médicas de Shiraz, Irán. El estudio fue aprobado por el comité de ética de la Universidad de Ciencias Médicas de Shiraz. Resultados: Se evaluaron cuarenta niños con una edad media de (10,8±4 años). El síntoma más común al ingreso fue dolor epigástrico (82,5%) con una duración media de síntomas de (16±14,5 meses). El hallazgo endoscópico más común fue enrojecimiento y erosión del antro (55%) y el hallazgo patológico más común fue gastritis crónica (77,5%). El evento adverso más común fue náusea (22,5%). La tasa de erradicación de la terapia secuencial fue 82,5%. Conclusión: La tasa de erradicación de la terapia secuencial fue de 82,5% en nuestros casos.

Erradicación de Helicobacter pylori con terapia triple estándar de primera línea / Helicobacter pylori eradication with standard first-line triple therapy

La infección por Helicobacter pylori es una de las infecciones crónicas más comunes a nivel mundial y causa importante de enfermedad péptica y cáncer gástrico. Infecta al 50% de la población adulta con mayor prevalencia en América Central/Sur y Asia y al menos dos veces mayor en poblaciones con alta incidencia de cáncer gástrico. Los objetivos de esta investigación fueron identificar la tasa de erradicación de H. pylori con terapia triple estándar y las posibles características asociadas a su erradicación. Se estudió a 119 pacientes con diagnóstico de infección por H. pylori, seleccionados en forma consecutiva de la consulta externa de Gastroenterología del Hospital General San Juan de Dios. Se realizó endoscopia diagnóstica y toma de biopsia gástrica. Se dio terapia triple estándar con lansoprazol, amoxicilina y claritromicina durante 10 días, seguido de 30 días con lansoprazol. Seis semanas después de completado el tratamiento se evaluó el antígeno de H. pylori en heces para determinar si hubo erradicación. La edad promedio de los participantes fue 49.0 años, 81.5% mujeres, 85.7% de área urbana, el síntoma más común fue dispepsia en 86.6%. En el examen post tratamiento el 89.9%, IC 95% [83.0, 94.7] presentó antígeno en heces negativo. No se encontró asociación entre las características de los pacientes con la respuesta al tratamiento. En conclusión, la respuesta a la terapia triple de primera línea se encuentra dentro del rango aceptable para continuar con ese esquema, pero debe mantenerse una evaluación constante por la presencia de posible resistencia.

Infection by Helicobacter pylori is one of the most common chronic infections worldwide and an important cause of peptic disease and gastric cancer. It infects 50% of the adult population with the highest prevalence in Central / South America and Asia and at least twice as high in populations with a high incidence of gastric cancer. The objectives of this research were to identify the eradication rate of H. pylori after first line standard triple therapy and the possible characteristics associated with its eradication. It was studied 119 patients with a diagnosis of H. pylori infection, selected consecutively from the outpatient department of Gastroenterology of the San Juan de Dios General Hospital. Diagnostic endoscopy and gastric biopsy was performed. Standard triple therapy was given with lansoprazole, amoxicillin and clarithromycin for 10 days, followed by 30 days with lansoprazole. Six weeks after the treatment was completed, the H. pylori antigen in feces was evaluated to determine if there was eradication. The average age of the participants was 49.0 years, 81.5% women, 85.7% of urban area, the most common symptom was dyspepsia in 86.6%. In the post-treatment examination 89.9%, 95% CI [83.0, 94.7] presented negative antigen in feces. No association was found between the characteristics of the patients with the response to treatment. In conclusion, the response to first line triple therapy is within the acceptable range to continue with this scheme, but a constant evaluation must be maintained due to the presence of possible resistance.

The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen / 대한소화기학회지

BACKGROUND/AIMS: Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. METHODS: We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). RESULTS: The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00–12.32; p=0.05). CONCLUSIONS: Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.

Therapeutic endoscopy in combination with quadruple therapy in treating bleeding caused by gastric ulcer

Objective: To analyze the efficacy of therapeutic endoscopy in combination with quadruple therapy in treating bleeding caused by gastric ulcer and investigate the factors inducing rebleeding

Methods: Two hundred and twelve patients with bleeding caused by gastric ulcer who were admitted to Binzhou People's Hospital, Shandong, China between April 2015 and April 2016 were selected as research subjects. The patients were randomly divided into a control group and an experimental group. Patients in the control group were treated by quadruple therapy, while patients in the observation group received therapeutic endoscopy treatment in addition to the same treatment as the control group. The treatment efficacy, adverse reaction, H pylori [Hp] clearance rate and rebleeding were compared between the two groups

Results: The effective rate of the observation group was 98.1%, which was significantly higher than that of the control group [80.2%], and the difference had statistical significance [P<0.05]. The incidence of adverse reactions in the observation group was lower than that in the control group. The Hp clearance rate of the observation group was higher than that of the control group, and the difference had statistical significance [P<0.05]. The multi-factor analysis on rebleeding suggested that whether therapeutic endoscopy was performed or not, hemoglobin level and presence of peptic ulcer stage A1 were independent risk factors

Conclusion: Endoscopic treatment in combination with quadruple therapy is better in the treatment of bleeding caused by gastric ulcer as compared to medical treatment alone. Patients with high-risk factors such as low content of hemoglobin and ulcer at stage A1 should be monitored more carefully to prevent the occurrence of rebleeding

Effect of a Proton Pump Inhibitor on Tumor Bleeding Prevention in Unresectable Gastric Cancer Patients: a Double-Blind, Randomized, Placebo-Controlled Trial

PURPOSE: Tumor bleeding is a major complication in inoperable gastric cancer. The study aim was to investigate the effects of proton pump inhibitor (PPI) treatment for the prevention of gastric tumor bleeding. MATERIALS AND METHODS: This study was a prospective double-blind, randomized, placebo-controlled trial. Patients with inoperable gastric cancer were randomly assigned to receive oral lansoprazole (30 mg) or placebo daily. The primary endpoint was the occurrence of tumor bleeding, and the secondary endpoints were transfusion requirement and overall survival (OS). RESULTS: This study initially planned to enroll 394 patients, but prematurely ended due to low recruitment rate. Overall, 127 patients were included in the analyses: 64 in the lansoprazole group and 63 in the placebo group. During the median follow-up of 6.4 months, tumor bleeding rates were 7.8% and 9.5%, in the lansoprazole and placebo groups, respectively, with the cumulative bleeding incidence not statistically different between the groups (P=0.515, Gray's test). However, during the initial 4 months, 4 placebo-treated patients developed tumor bleeding, whereas there were no bleeding events in the lansoprazole-treated patients (P=0.041, Gray's test). There was no difference in the proportion of patients who required transfusion between the groups. The OS between the lansoprazole (11.7 months) and the placebo (11.0 months) groups was not statistically different (P=0.610). Study drug-related serious adverse event or bleeding-related death did not occur. CONCLUSIONS: Treating patients with inoperable gastric cancer with lansoprazole did not significantly reduce the incidence of tumor bleeding. However, further studies are needed to evaluate whether lansoprazole can prevent tumor bleeding during earlier phases of chemotherapy (ClinicalTrial.gov, identifier No. NCT02150447).

Informe de evaluación científica basada en la evidencia disponible: colitis ulcerosa / Scientific evaluation report based on available evidence: ulcerative colitis

INTRODUCCIÓN: La colitis ulcerosa es una enfermedad inflamatoria crónica que afecta la mucosa del colon en forma continua, comprometiendo el recto y una porción variable de la extensión del resto del colon, sin la presencia de granulomas en la biopsia. En esta enfermedad, el sistema inmune reconoce esta porción del colon como ajena al cuerpo y lo ataca generando úlceras que caracterizan a esta enfermedad. TECNOLOGÍAS SANITARIAS ANALIZADAS: Adalimumab, azatioprina, golimumab, infliximab, mesalazina, lansoprazol, omeprazol, sulfasalazina y colestiramina. EFICACIA DE LOS TRATAMIENTOS: Se extrajeron 31 revisiones sistemáticas que incluyen 11 ensayos controlados aleatorizados que evaluaban la eficacia de adalimumab, golimumab e infliximab en pacientes con colitis ulcerosa moderada a grave. El tratamiento con adalimumab aumenta ligeramente el número de pacientes que cicatrizan su mucosa e incrementan su score IBDQ (calidad de vida) en más de 12 puntos, a las 8 semanas. El tratamiento con golimumab probablemente aumenta el número de pacientes que responden clínicamente a las 6 semanas, mientras que probablemente aumenta ligeramente el número de pacientes que remite y cicatrizan su mucosa a las 6 semanas. Además, golimumab probablemente no genera diferencias en cuanto a la calidad de vida (cuestionario IBDQ) de pacientes con colitis ulcerosa. El tratamiento con infliximab aumenta el número de pacientes que presentan respuesta clínica a las 8 semanas, mientras que reduce ligeramente el número de pacientes que reciben colectomía a las 54 semanas. No se encontró evidencia de eficacia de los tratamientos sobre una menor hospitalización o una menor estadía hospitalaria, ni estudios que evaluaran la eficacia en niños con colitis ulcerosa. ANÁLISIS ECONÓMICO: Infliximab resultó ser la alternativa que presentó mayor efectividad. Sin embargo, la efectividad incremental en relación a adalimumab es sólo de 0,66 QALYs, superándolo en costes en aproximadamente un 45%. Infliximab y golimumab fueron los tratamientos que presentaron mayor costo en relación a adalimumab. En esto se incluyen los costos de efectos adversos serios, porcentaje de pacientes que se sometían a colectomía mientras estaban en terapia con algún biológico y los costos de administración de infliximab. Para este último se consideró un costo mayor, ya que como su administración es intravenosa se deben considerar las horas en que el paciente debe estar en una sala de observaciones para que se le administre el biológico. En cuanto a las agencias internacionales, Inglaterra recomienda el uso de adalimumab, infliximab o golimumab en pacientes con colitis ulcerosa moderada a grave, siempre y cuando la terapia convencional no funcione o no sea la adecuada. El impacto presupuestario calculado para el primer año de tratamiento fue de MM$1.810 para adalimumab, $MM2.424 para infliximab, y MM$353.378 para golimumab. CONCLUSIÓN: Para dar cumplimiento al artículo 28° del Reglamento que establece el proceso destinado a determinar los diagnósticos y tratamientos de alto costo con Sistema de Protección Financiera, según lo establecido en los artículos 7°y 8° de la ley N°20.850, aprobado por el decreto N°13 del Ministerio de Salud, se concluye que el presente informe de evaluación se considera favorable, de acuerdo a lo establecido en el Título III. de las Evaluaciones Favorables de la Norma Técnica N° 0192 de este mismo ministerio.

Improving the standard sequential treatment of Helicobacter pylori with either extended treatment or by adding bismuth

Background and study aims: Standard sequential treatment for Helicobacter pylori [H. pylori] eradication has less success because of increasing clarithromycin resistance. Extended treatment and bismuth containing regimens were, therefore, investigated

Patients and methods: Consecutive H. pylori-positive patients with dyspepsia were randomly allocated to one of the three sequential regimens: The first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first 5 days, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second 5 days [standard sequential, SS]. The second group was given the same regimen but for 7 + 7 days instead of 5 + 5 days [extended sequential, ES]. In the third group, colloidal bismuth 600 mg b.i.d. was added to the second regimen for 14 days [extended sequential + bismuth subcitrate, ES + B]. Urea breath test or histology was performed before enrolment and 6 weeks after the end of treatment to detect H. pylori

Results: A total of 280 patients were included in the study. Per-protocol eradication rates were 62% [56/90], 72% [56/78], and 75% [54/72] in patients who received SS, ES, and ES + B regimens, respectively. Moreover, intention-to-treat eradication rates were 53% [56/104], 62% [56/90] and 62% [54/86], respectively. The differences in eradication rates between the groups were not statistically significant

Conclusion: Although prolonging of the sequential treatment to 14 days may be considered, addition of bismuth to the regimen is of no avail

Comparison on Oral versus Intravenous Proton Pump Inhibitors for Prevention of Bleeding after Endoscopic Submucosal Dissection of Gastric Lesions / 대한소화기학회지

BACKGROUND/AIMS: Although intravenous proton pump inhibitor (PPI) has been used for the prevention of post endoscopic submucosal dissection (ESD) bleeding, the route of administration has not been confirmed. The aim of the present study was to compare the efficacy of intravenous and oral PPI administration for the prevention of delayed post ESD bleeding. METHODS: Total 166 consecutive patients were randomly assigned to 30 mg lansoprazol twice a day (PO group) and 120 mg pantoprazole intravenous injection (IV group) for 48 hours. Finally, 65 patients in PO group and 87 patients in IV group were analyzed. After ESD, all patients underwent follow up endoscopy after 24 hours and were observed the symptoms of bleeding up to 60 days after ESD. RESULTS: Age, sex and use of anticoagulants were not different between groups. At follow up endoscopy after 24 hours, oozing and exposed vessel was noted in 4.6% of PO group and 8.0% of IV group and there was no significant difference. Delayed bleeding occurred in 4 of 65 patients (6.2%) in the PO group and 8 of 87 patients (9.2%) in the IV group (p>0.999). By multivariate analysis, oozing or exposed vessels at follow up endoscopy were risk factors for delayed bleeding (OR=17.5, p=0.022). CONCLUSIONS: There was no significant difference in the delayed bleeding, length of hospital stay according to the administration route. Bleeding stigmata at follow up endoscopy was risk factor of delayed bleeding. Oral PPI administration can cost-effectively replace IV PPI for prevention of post ESD bleeding.

PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. METHODS: The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. RESULTS: As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. CONCLUSIONS: These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

Effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites in rats

abstract The aim of this study was to evaluate the effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites. Rats were intragastrically administered caffeine (30 mg·kg-1, once per day), tea polyphenol (400 mg·kg-1, once per day) or daidzein (13.5 mg·kg-1, once per day) for 14 days, followed by an intragastric administration of lansoprazole (8 mg·kg-1) on the 15th day. The plasma concentrations of lansoprazole and its two primary metabolites, 5-hydroxylansoprazole and lansoprazole sulfone, were determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Tea polyphenol significantly elevated the Area Under the Curve (AUC) of lansoprazole from 680.29 ± 285.99 to 949.76 ± 155.18 μg/L.h and reduced that of lansoprazole sulfone from 268.82 ± 82.37 to 177.72 ± 29.73 μg/L.h. Daidzein increased the AUC of lansoprazole from 680.29 ± 285.99 to 1130.44 ± 97.6 μg/L.h and decreased that of lansoprazole sulfone from 268.82 ± 82.37 to 116.23 ± 40.14 μg/L.h. The pharmacokinetics of 5-hydroxylansoprazole remained intact in the presence of tea polyphenol or daidzein. Caffeine did not affect the pharmacokinetics of lansoprazole and its metabolites. The results imply that tea polyphenol and daidzein may inhibit the in vivo metabolism of lansoprazole by suppressing CYP3A.

resumo O objetivo deste estudo foi avaliar os efeitos da cafeína, do polifenol do chá e da daidzeína na farmacocinética do lansoprazol e de seus metabólitos. Administraram-se, intragastricamente, aos ratos cafeína (30 mg·kg-1, uma vez ao dia), polifenol do chá(400 mg·kg-1, uma vez ao dia) ou daidzeína (13,5 mg·kg-1, uma vez ao dia), por 14 dias, seguindo-se a administração de lansoprazol (8 mg·kg-1) no 15º. dia. As concentrações plasmáticas do lansoprazol e de seus dois metabólitos primários, 5-hidroxilansoprazol e sulfona de lansoprazol, foram determinadas por cromatografia líquida de alta eficiência acoplada com espectrometria de massas (CLAE-EM/EM). O polifenol do chá elevou, significativamente, a Área Sob a Curva (ASC) do lansoprazol de 680,29 ± 285,99 para 949,76 ± 155,18 μg/L.h e reduziu a da sulfona de lansoprazol de 268,82 ± 82,37 para 177,72 ± 29,73 μg/L.h. A daidzeína aumentou a ASC do lansoprazol de 680,29 ± 285,99 para 1130,44 ± 97,6 μg/L.h e reduziu a da sulfona de lansoprazol de 268,82 ± 82,37 para 177,72 ± 29,73 μg/L.h. A farmacocinética do 5-hidroxilansoprazol permaneceu intacta na presença de polifenol do chá ou daidzeína. A cafeína não afetou a farmacocinética do lansoprazol e de seus metabólitos. Os resultados sugerem que o polifenol do chá e a daidzeína podem inibir o metabolismo in vivo do lansoprazol por supressão da CYP3A.

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.

Anaphylaxis to lansoprazole with tolerance to other proton pump inhibitors

Anaphylaxis to proton pump inhibitors (PPIs) has rarely been reported. Different patterns of cross-reactivity between PPIs have also been demonstrated using skin tests. Here, we report a case of anaphylaxis to lansoprazole with tolerance to other commercially available PPIs, which was proved by skin tests and oral provocation tests (OPTs). A 47-year-old female patient visited our Emergency Department with a sudden onset of whole body urticaria, facial swelling, dyspnea, and loss of consciousness that developed 1 hour after ingestion of 30 mg of lansoprazole for her episodic epigastric soreness. The skin prick test (SPT) and the intradermal test (IDT) with lansoprazole, esomeprazole, rabeprazole, and pantoprazole were performed. Lansoprazole showed positive reactions in both the SPT (3 mg/mL) and the IDT (0.003 mg/mL). Rabeprazole (3 mg/mL) showed a positive reaction only in IDT. The SPT and the IDT with esomeprazole and pantoprazole were all negative. The OPT with 30 mg of lansoprazole was positive (showing generalized rash and facial swelling 30 minuites after ingestion), while OPTs with esomeprazole, pantoprazole, and rabeprazole were all negative. Other PPIs could be safe alternatives in cases of anaphylaxis to 1 PPI. Skin tests seem to be helpful to define cross-reactivity between PPIs.