RESUMEN
We hereby describe a rare case of levosulpiride-induced atypical parkinsonism presenting with sluggish movements, atypical kinetic tremors (tremors with voluntary movement), periorbital tremors, dystonia, difficulty in speech and coordination, postural imbalance, with additional features of difficulty in swallowing and drooling with associated recent onset psychiatric disturbances such as anxiety and low-lying depression. The dechallenge of levosulpiride and medications for associated anxiety and low-lying depression caused a complete remission of the disease within 2 ½ months.
Asunto(s)
Depresión , Sulpirida/análogos & derivados , Temblor , Humanos , Temblor/inducido químicamente , Rabeprazol/efectos adversos , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Ansiedad , Combinación de MedicamentosRESUMEN
BACKGROUND: A cure for Helicobacter pylori (H. pylori) remains a problem of global concern. The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide. Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy, tolerability and cost. The most common sequential therapy consists of a dual therapy [proton-pump inhibitors (PPIs) and amoxicillin] for the first period (5 to 7 d), followed by a triple therapy for the second period (PPI, clarithromycin and metronidazole). PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics, hence the idea of using new generation molecules. AIM: To compare an optimized sequential therapy with the standard non-bismuth quadruple therapies of 10 and 14 d, in terms of efficacy, incidence of adverse effects (AEs) and cost. METHODS: This open-label prospective study randomized 328 patients with confirmed H. pylori infection into three groups (1:1:1): The first group received quadruple therapy consisting of twice-daily (bid) omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg for 10 d (QT-10), the second group received a 14 d quadruple therapy following the same regimen (QT-14), and the third group received an optimized sequential therapy consisting of bid rabeprazole 20 mg plus amoxicillin 1 g for 7 d, followed by bid rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the next 7 d (OST-14). AEs were recorded throughout the study, and the H. pylori eradication rate was determined 4 to 6 wk after the end of treatment, using the 13C urea breath test. RESULTS: In the intention-to-treat and per-protocol analysis, the eradication rate was higher in the OST-14 group compared to the QT-10 group: (93.5%, 85.5% P = 0.04) and (96.2%, 89.5% P = 0.03) respectively. However, there was no statistically significant difference in eradication rates between the OST-14 and QT-14 groups: (93.5%, 91.8% P = 0.34) and (96.2%, 94.4% P = 0.35), respectively. The overall incidence of AEs was significantly lower in the OST-14 group (P = 0.01). Furthermore, OST-14 was the most cost-effective among the three groups. CONCLUSION: The optimized 14-d sequential therapy is a safe and effective alternative. Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Metronidazol/efectos adversos , Claritromicina/efectos adversos , Rabeprazol/efectos adversos , Estudios Prospectivos , Quimioterapia Combinada , Antibacterianos/efectos adversos , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Amoxicilina/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
Proton pump inhibitors (PPIs) have recently been reported to be linked with nephrotoxicity. PPIs are metabolized mainly or partly by cytochrome P450 2C19 (CYP2C19). However, the relationship between CYP2C19 genetic polymorphism and PPI-induced nephrotoxicity is unclear. In this study, we aimed to analyze the association between the time of occurrence of renal injury by PPIs, including lansoprazole, esomeprazole, rabeprazole, and vonoprazan, and CYP2C19 metabolizer status classified by CYP2C19 genotypes. Patients prescribed PPIs were reviewed in this retrospective cohort study. The primary outcome was the time to a 30% decrease in estimated glomerular filtration rate (eGFR) from baseline. In patients treated with lansoprazole, the time to a 30% decrease in eGFR for the CYP2C19 poor metabolizer (PM) group was significantly shorter than that for the non-PM group (hazard ratio for PM vs. non-PM, 2.43, 95% confidence interval, 1.21 to 4.87, P = 0.012). In contrast, in patients that received esomeprazole, rabeprazole, or vonoprazan, no significant differences were found in the time to a 30% decrease in eGFR between non-PM and PM groups. The adjusted hazard ratios for the time to a 30% eGFR decrease in patients treated with lansoprazole were significantly higher for CYP2C19 PM, hypertension, and a history of myocardial infarction. In conclusion, this retrospective study showed that CYP2C19 metabolizer status was associated with the time to a 30% eGFR decrease in patients treated with lansoprazole, but not with esomeprazole, rabeprazole, or vonoprazan.
Asunto(s)
Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Citocromo P-450 CYP2C19/genética , Esomeprazol/efectos adversos , Genotipo , Riñón/metabolismo , Lansoprazol , Inhibidores de la Bomba de Protones/efectos adversos , Rabeprazol/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan-amoxicillin (VA) and 14-day rabeprazole-amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. METHODS: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. RESULTS: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). CONCLUSIONS: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Rabeprazol/efectos adversos , Estudios Prospectivos , Inhibidores de la Bomba de Protones/efectos adversos , Claritromicina/uso terapéutico , Quimioterapia Combinada , Antibacterianos/efectos adversos , Amoxicilina/efectos adversos , Resultado del TratamientoRESUMEN
Rabeprazole is a representative of proton pump inhibitors and widely used in anti-ulcer treatment. However, the effect of Rabeprazole on gut barrier function remains to be identified. In this study, we show that ZO-1 expression is decreased in patients receiving Rabeprazole by immunofluorescence (IF) analysis. Western blotting (WB) and real-time PCR (qPCR) results demonstrate that Rabeprazole treatment leads to a significant downregulation of ZO-1 expression through inhibition of the FOXF1/STAT3 pathway, leading to destroy barrier function, which illustrates a novel pathway that Rabeprazole regulates barrier function in gastric epithelial cells. Mechanistically, Rabeprazole treatment led to a downregulation of STAT3 and FOXF1 phosphorylation, leading to inhibit nuclear translocation and decrease the binding of STAT3 and FOXF1 to ZO-1 promoter, respectively. Most important, endogenous FOXF1 interacted with STAT3, and this interaction was dramatically abolished by Rabeprazole stimulation. Overexpression of STAT3 and FOXF1 in GES-1 cells reversed the inhibitory effect of Rabeprazole on ZO-1 expression, respectively. These finding extended the function of Rabeprazole and established a previously unappreciated mechanism by which the Rabeprazole/FOXF1/STAT3 axis facilitated ZO-1 expression to regulate barrier function, and a comprehensive consideration and evaluation was required in treatment of patients.
Asunto(s)
Células Epiteliales , Rabeprazol , Transducción de Señal , Humanos , 2-Piridinilmetilsulfinilbencimidazoles/metabolismo , Células Epiteliales/metabolismo , Factores de Transcripción Forkhead/metabolismo , Rabeprazol/efectos adversos , Rabeprazol/metabolismo , Factor de Transcripción STAT3/metabolismo , Estómago , Proteína de la Zonula Occludens-1/efectos de los fármacos , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Background/Aims: Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in Korea. However, real-world clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and rabeprazole-based triple therapy. Methods: We retrospectively reviewed data from patients who received first-line treatment for H. pylori infection using tegoprazan- or rabeprazole-based triple therapy for 2 weeks (50 mg tegoprazan or 20 mg rabeprazole+1,000 mg amoxicillin+500 mg clarithromycin twice daily). The primary endpoint was the eradication rate as determined by intention-to-treat analysis. Results: Of the 677 patients included in our study, 344 and 333 received tegoprazan-based and rabeprazole-based triple therapy, respectively. The eradication rate from intention-to-treat analysis was 76.7% (95% confidence interval [CI], 72.1% to 81.0%) for tegoprazan-based triple therapy and 75.4% (95% CI, 70.5% to 79.8%) for rabeprazole-based triple therapy. There was no significant difference in the eradication rates between the two groups (p>0.999). Per-protocol analysis also revealed no significant difference between the eradication rates of the two groups (tegoprazan 83.4% [95% CI, 79.0% to 87.2%] vs rabeprazole 83.5% [79.0% to 87.4%], p>0.999). Furthermore, there was no significant difference in adverse event rates between the two groups (tegoprazan, 27.6%; rabeprazole, 25.8%; p=0.604). Conclusions: The eradication rate of tegoprazan-based triple therapy was similar to that of rabeprazole-based triple therapy. Further studies on the dose-escalation effect of tegoprazan for H. pylori eradication and the efficacy of tegoprazan in regimens other than conventional triple therapy are needed.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Gastropatías , Humanos , Amoxicilina , Antibacterianos/efectos adversos , Claritromicina , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Inhibidores de la Bomba de Protones , Rabeprazol/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To estimate the effectiveness and safety of triple therapy containing berberine, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori (H. pylori). METHODS: This prospective, randomized controlled, open-label, noninferiority trial included treatment-naive patients with H. pylori infection who were randomly allocated at a ratio of 1:1 into the berberine triple therapy group (berberine hydrochloride 300 mg thrice daily, amoxicillin 1 g twice daily, and rabeprazole 10 mg twice daily) or standard bismuth-containing quadruple therapy group (amoxicillin 1 g twice daily, rabeprazole 10 mg twice daily, clarithromycin 500 mg twice daily, and bismuth tartrate 200 mg twice daily) for 14 days. Negative 13 C/14 C-urea breath test at 4 weeks after completion of the therapy was regarded as successful eradication. RESULTS: Altogether 262 and 262 patients received berberine triple therapy and bismuth-containing quadruple therapy, respectively. Both intention-to-treat (79.8% vs 80.9%, P = 0.742) and per-protocol analyses (83.6% and 85.1%, P = 0.636) showed comparable eradication rate between the two groups, indicating a noninferior eradication rate (the lower limit of the 95% confidence interval over -10% [-7.9% and -7.87%, respectively]). Adverse events more commonly occurred in the bismuth-containing quadruple-therapy group (8.8% vs 16.0%, P = 0.012), while patient compliance and symptom improvement of the two regimens were comparable. CONCLUSION: Triple therapy containing berberine, amoxicillin and rabeprazole is noninferior to bismuth-containing quadruple therapy in the initial treatment for H. pylori eradication.
Asunto(s)
Berberina , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/efectos adversos , Rabeprazol/efectos adversos , Bismuto/uso terapéutico , Antibacterianos/efectos adversos , Berberina/efectos adversos , Estudios Prospectivos , Inhibidores de la Bomba de Protones/efectos adversos , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Claritromicina/efectos adversos , Resultado del TratamientoRESUMEN
To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)-related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75â mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant (P < 0.05). On comparing the groups, the differences between the control group and the rabeprazole group, those between the control group and the rabeprazole + rebamipide group, and those between the rebamipide group and the rabeprazole + rebamipide group were found to be statistically significant (P < 0.05). The severity of the upper gastrointestinal hemorrhage in the rabeprazole group and the rabeprazole + rebamipide group was significantly lower than that in the control group. The 4 groups exhibited no significant differences in the incidence of MACEs (P > 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.
Asunto(s)
Enfermedad Coronaria , Intervención Coronaria Percutánea , Anciano , Humanos , Rabeprazol/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia Gastrointestinal/tratamiento farmacológicoRESUMEN
BACKGROUND: Proton pump inhibitors (PPIs), such as esomeprazole, pantoprazole, dexlansoprazole, and rabeprazole, are one of the most commonly prescribed medications. Several studies have linked the long-term use of PPIs to a potentially increased risk of gastric cancer. Therefore, this study aimed to determine the underlying mechanism of PPI-mediated gastric cancer. METHODS: Lysosomes were isolated using immunoprecipitation. The inhibition of vacuolar-type ATPase (V-ATPase) by PPIs was assayed using a PiColorLock Gold Phosphate Detection System. PPI-induced lysosomal stress was analyzed using transcription factor EB (TFEB) nuclear translocation. PPI-induced endoplasmic reticulum (ER) stress was analyzed using the expression of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). Finally, reactive oxygen species (ROS) removal was determined using the activity of superoxide dismutase (SOD). RESULTS: PPIs caused a 70% inhibition of V-ATPase activity at 20 µM, leading to lysosomal stress through TFEB nuclear translocation; ER stress by inducing the expression of PERK, IRE1, and ATF6; and enhanced SOD activity for ROS removal. CONCLUSION: The long-term use of PPIs inhibits lysosomal V-ATPase, leading to ER stress and ROS accumulation, which may result in an increased risk of gastric cancer. Because lysosomes and the ER are common organelles in cells, physicians prescribing PPIs for gastroesophageal reflux and peptic ulcer diseases should pay more attention to the general effects of these agents on the human body.
Asunto(s)
Estrés del Retículo Endoplásmico , Inhibidores de la Bomba de Protones , ATPasas de Translocación de Protón Vacuolares , Factor de Transcripción Activador 6/metabolismo , Dexlansoprazol/efectos adversos , Esomeprazol/efectos adversos , Humanos , Pantoprazol/efectos adversos , Proteínas Serina-Treonina Quinasas/metabolismo , Inhibidores de la Bomba de Protones/efectos adversos , Rabeprazol/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/inducido químicamente , Superóxido Dismutasa/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismoRESUMEN
BACKGROUND AND AIM: The influence of gastric acid inhibitors (GAIs) on nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is controversial. Herein, the influences of different GAIs on NSAID-induced intestinal injury and the underlying mechanisms are clarified. METHODS: Indomethacin (IND; 10 mg/kg/day) was administered to mice to induce small intestinal injury. Disease activity was examined macroscopically and histologically. The permeability of small intestine was evaluated by measuring plasma lipopolysaccharide levels. 16S rDNA sequencing was performed to determine the composition of intestinal flora. RESULTS: Among the four GAIs, ilaprazole (IPZ) significantly attenuated IND-induced small intestinal injury and maintained the integrity of the mucosal barrier. Omeprazole (OPZ) and vonoprazan (VPZ) ameliorated ulceration without significant differences, while rabeprazole (RPZ) failed to protect against the injury. To explore the potential mechanism, we investigated changes in the gut microbiota mediated by GAIs. After 5-day administration, GAIs significantly altered the composition of the gut microbiota. The IND group had a significant decrease in alpha diversity compared with the control group, and this decrease was reversed by OPZ and IPZ treatment, respectively. After IPZ treatment, the community membership was more assembled in the control group than the IND group. Further, we found that Lactobacillus was significantly increased in the groups of OPZ, IPZ, and VPZ, while Bacteroides was significantly increased in the RPZ group. CONCLUSION: Our results indicated that GAIs have different influences on the mucosal barrier, possibly by altering the composition of intestinal microbiota, and the impacts mediated by various GAIs in the IND-induced intestinal damage model seem different.
Asunto(s)
Indometacina , Enfermedades Intestinales , 2-Piridinilmetilsulfinilbencimidazoles , Animales , Antiinflamatorios no Esteroideos/efectos adversos , ADN Ribosómico , Indometacina/efectos adversos , Enfermedades Intestinales/patología , Mucosa Intestinal/patología , Intestino Delgado/patología , Lipopolisacáridos , Ratones , Omeprazol/efectos adversos , Potasio , Inhibidores de la Bomba de Protones/efectos adversos , Pirroles , Rabeprazol/efectos adversos , SulfonamidasRESUMEN
Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder characterized by prolonged inflammation of the gastrointestinal tract. IBD can result from gut barrier dysfunction, altered gut microbiota, and abnormal intestinal immunity induced by environmental factors in genetically susceptible individuals. Proton pump inhibitors (PPIs) such as rabeprazole are frequently employed for gastric acid inhibition. However, long-term PPI administration can alter the intestinal microbiome composition, possibly worsening IBD severity. The present study revealed that tegoprazan, a potassium-competitive acid blocker, significantly improved colitis in mice and enhanced the intestinal epithelial barrier function. Tegoprazan alleviated gut microbiota dysbiosis and enhanced the growth of Bacteroides vulgatus. In turn, B. vulgatus alleviated intestinal inflammation by inhibiting epithelial adhesion of pathogenic bacteria. Unlike rabeprazole, tegoprazan did not induce gut dysbiosis. Our findings provide novel insights into the potential role of tegoprazan as an intestinal protectant for IBD and as a therapeutic agent for gastric acid-related diseases.
Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Animales , Derivados del Benceno , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Disbiosis/microbiología , Imidazoles , Inflamación , Ratones , Potasio , Inhibidores de la Bomba de Protones/farmacología , Rabeprazol/efectos adversosRESUMEN
Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.
Asunto(s)
Lesión Renal Aguda , Antineoplásicos , Lesión Renal Aguda/patología , Animales , Antineoplásicos/farmacología , Apoptosis , Cisplatino/efectos adversos , Células HEK293 , Humanos , Riñón/metabolismo , Ratones , Necroptosis , Rabeprazol/efectos adversosRESUMEN
BACKGROUND/AIM: Concomitant proton pump inhibitor (PPI) and immune checkpoint inhibitor (ICPI) were determined as risk factors of acute kidney injury. To identify the type of PPI associated with ICPI-induced nephritis, we used the Japanese Adverse Drug Event Report database. PATIENTS AND METHODS: ICPIs (nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, and avelumab) and PPIs (esomeprazole, omeprazole, vonoprazan, rabeprazole, and lansoprazole) were selected as suspected nephritis-inducing drugs. RESULTS: The cases of concomitant use of atezolizumab and rabeprazole, ipilimumab and omeprazole, ipilimumab and lansoprazole, nivolumab and esomeprazole, nivolumab and omeprazole, nivolumab and rabeprazole, nivolumab and lansoprazole, pembrolizumab and esomeprazole, as well as pembrolizumab and lansoprazole had a significantly higher reported odds ratio than monotherapy cases. CONCLUSION: Male patients or patients using ICPIs and PPIs (excluded vonoprazan) concomitantly should be monitored for renal function after chemotherapy.
Asunto(s)
Nefritis , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de Puntos de Control Inmunológico , Masculino , Omeprazol , Inhibidores de la Bomba de Protones/efectos adversos , Rabeprazol/efectos adversosRESUMEN
BACKGROUND AND AIM: Recent evidence has concerned acute kidney injury (AKI) after the proton pump inhibitor (PPI) application. There are few real-world studies to compare the occurrences, clinical features, and prognosis of AKI related to various PPI regimens. We aimed to evaluate and compare the links between different PPIs and AKI in a large population by investigating the Food and Drug Administration Adverse Event Reporting System (FAERS) until recently. METHODS: Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected AKI after different PPIs based on the FAERS from January 2004 to December 2019. The times to onset, fatality, and hospitalization rates of PPI-associated AKI were also investigated. RESULTS: We identified 19 522 PPI-associated AKIs, which appeared to influence more middle-aged patients than elderly ones (53.04% vs 33.94%). Women were more affected than men (55.42% vs 44.58%). Lansoprazole appeared a stronger AKI association than other PPIs, based on the highest reporting odds ratio (reporting odds ratio = 20.8, 95% confidence interval = 20.16, 21.46), proportional reporting ratio (proportional reporting ratio = 15.55, χ2 = 73 899.68), and empirical Bayes geometric mean (empirical Bayes geometric mean = 15.15, 95% confidence interval = 14.76). The median time to AKI onset was 446 (interquartile range [IQR] 16-2176) days after PPI administration. PPIs showed a significant difference in average time to AKI onset (P < 0.001), with the shortest of 9 (IQR 3-25) days for rabeprazole and the longest of 1221 (IQR 96.5-2620) days for esomeprazole. PPI-associated AKI generally led to a 5.69% fatality rate and an 8.94% hospitalization rate. The highest death rate occurred in rabeprazole (15.35%). CONCLUSIONS: Based on the FAERS database, we profiled AKI related to various PPIs with more details in occurrences, clinical characteristics, and prognosis. Concern should be paid for PPIs when applied to patients with a tendency for AKI.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Sistemas de Registro de Reacción Adversa a Medicamentos , Vigilancia de Productos Comercializados/métodos , Inhibidores de la Bomba de Protones/efectos adversos , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/prevención & control , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Esomeprazol/administración & dosificación , Esomeprazol/efectos adversos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Lansoprazol/administración & dosificación , Lansoprazol/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/administración & dosificación , Rabeprazol/administración & dosificación , Rabeprazol/efectos adversos , Factores Sexuales , Adulto JovenRESUMEN
The treatment regimen for the eradication of Helicobacter pylori may be best when therapy is susceptibility guided. However, it is unrealistic to use a strategy based on susceptibility testing to prioritize therapy for every patient in China. Empirical therapy of H. pylori is still widely used. The study was designed to discuss the best first-line treatment regimen depending on empirical therapy. The focal point of the study was the optimal length of the therapy. Also, the selection of antibiotics was discussed in the article. This was a prospective, randomized, non-inferiority trial. H. pylori-infected patients who have no previous eradication therapy were randomly assigned to the following: 20 mg of rabeprazole, 1000 mg of amoxicillin, 500 mg of clarithromycin, and 220 mg of bismuth potassium citrate (BACPPI), administered twice a day for 10 or 14 days. The efficacy, side effects, and remission rate of clinical symptoms were determined. A total of 240 subjects were included in the study. The eradication rate with 14 and 10 days was essentially identical in both intention-to-treat (90.83% [95% CI, 86%-96%] vs. 87.50% [95% CI, 82%-93%]) and per-protocol (94.78% [95% CI, 91%-99%] vs. 92.11% [95% CI, 87%-97%]) analyses. Loss of appetite and belching symptoms were significantly better in the BACPPI-10 group than those in the control group after treatment. Side effects were generally mild and similar between groups. Our results showed that a 10-day amoxicillin-clarithromycin-containing bismuth quadruple therapy may be recommended for the primary empirical treatment of H. pylori infection in Beijing, China.
Asunto(s)
Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Adulto , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Antibacterianos/efectos adversos , Antiulcerosos/efectos adversos , China , Claritromicina/efectos adversos , Claritromicina/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/efectos adversos , Compuestos Organometálicos/uso terapéutico , Estudios Prospectivos , Rabeprazol/efectos adversos , Rabeprazol/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The effects of PPIs on human sperm fertilizing capacity were poorly investigated although these drugs are widely over-used. Two publications retrospectively studied relationships between any PPI intake and sperm parameters from patients consulting at infertility clinics, but the conclusions of these reports were contradictory. Only two reports investigated the effects of lansoprazole and omeprazole on sperm motility and found lansoprazole to be deleterious and omeprazole to be neutral for sperm motility. The inconsistency of the PPI effect in the previous reports emphasizes the need for more basic research on human spermatozoa, taking into account the hypothesis that the different PPI drugs may have different effects on sperm physiology. OBJECTIVES: Do PPIs, which are among the most widely sold drug in the word, impact negatively human sperm capacitation and sperm motility? MATERIALS AND METHODS: The effects of PPIs on human sperm maturation and motility were analyzed by CASA, flow cytometry, and Western blot. RESULTS: We tested the impact of 6 different PPIs on human sperm motility and capacitation. We showed that pantoprazole, but not the other PPIs, decreased sperm progressive motility and capacitation-induced sperm hyperactivation. We therefore investigated further the effects of pantoprazole on sperm capacitation, and we observed that it had a significant deleterious effect on the capacitation-induced hyperpolarization of the membrane potential and capacitation-associated protein phosphorylation. DISCUSSION AND CONCLUSION: Our results indicate that exposure to pantoprazole has an adverse effect on the physiological competence of human spermatozoa. As the capacitation process takes place within the female tract, our results suggest that PPIs intake by the female partner may impair in vivo sperm maturation and possibly fertilization. Moreover, the absence of adverse effect by PPIs on mouse sperm emphasizes the need to develop reprotox assays using human material to better assess the effects of medication intake on sperm physiology.
Asunto(s)
Pantoprazol/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Análisis de Semen/métodos , Capacitación Espermática/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , 2-Piridinilmetilsulfinilbencimidazoles/efectos adversos , 2-Piridinilmetilsulfinilbencimidazoles/farmacología , Adulto , Fertilización/efectos de los fármacos , Humanos , Lansoprazol/efectos adversos , Lansoprazol/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Persona de Mediana Edad , Omeprazol/efectos adversos , Omeprazol/farmacología , Pantoprazol/farmacología , Fosforilación/efectos de los fármacos , Inhibidores de la Bomba de Protones/farmacología , Rabeprazol/efectos adversos , Rabeprazol/farmacología , Estudios Retrospectivos , Maduración del Esperma/fisiología , Espermatozoides/fisiología , Adulto JovenRESUMEN
AIM: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection. METHODS: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori. RESULTS: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies. CONCLUSION: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.
Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Compuestos Organometálicos/uso terapéutico , Tetraciclina/uso terapéutico , Amoxicilina/efectos adversos , Antibacterianos/efectos adversos , Antiulcerosos/efectos adversos , Antiulcerosos/uso terapéutico , Farmacorresistencia Bacteriana , Quimioterapia Combinada/efectos adversos , Femenino , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Metronidazol/efectos adversos , Metronidazol/uso terapéutico , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Compuestos Organometálicos/efectos adversos , Cooperación del Paciente , Resistencia a las Penicilinas , Rabeprazol/efectos adversos , Rabeprazol/uso terapéutico , Tetraciclina/efectos adversos , Resistencia a la TetraciclinaRESUMEN
Fixed drug eruption is one of the most common forms of cutaneous adverse drug reactions. Analgesics and antibiotics are the most common drugs causing fixed drug eruption. Here, we report a case of multiple widespread fixed drug eruption caused by rabeprazole.
Asunto(s)
Erupciones por Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Gastritis/tratamiento farmacológico , Rabeprazol/efectos adversos , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Gastritis/diagnóstico , Humanos , Masculino , Rabeprazol/uso terapéuticoRESUMEN
Cutaneous adverse drug reactions (cADR) should be appropriately managed in drug administration. LANSAP® , Rabecure® and VONOSAP® are currently used for Helicobacter pylori eradication therapy. Here, we examined the characteristics of cADR caused by these drugs using data from the Pharmaceuticals and Medical Devices Agency (PMDA). Periods subject to analyses were set according to the year of release of these drugs: (i) from 2008 to 2017 for LANSAP; (ii) from 2014 to 2017 for Rabecure; and (iii) 2017 for VONOSAP. Among all cADR reported to the PMDA, those attributed to LANSAP, Rabecure and VONOSAP accounted for 2.3%, 1.0% and 3.6% of cases, respectively. cADR occurred in patients aged in their 20s or older, with the oldest patients aged in their 60s. Numbers of male and female patients were 28 and 70 for LANSAP, eight and 14 for Rabecure and three and 16 for VONOSAP, respectively. Statistical analyses revealed significant sex differences for LANSAP (P = 0.022) and VONOSAP (P = 0.012), but not for Rabecure (P = 0.729). LANSAP, Rabecure or VONOSAP caused erythema multiforme in the largest population of patients and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in three patients. Ratios of SJS/TEN were 0.0-5.3% for LANSAP, Rabecure or VONOSAP, but 11.5-44.8% for the corresponding single constituent drugs other than vonoprazan. In conclusion, female sex appears to represent a risk factor for cADR attributed to H. pylori eradication therapy using LANSAP or VONOSAP, although H. pylori eradication therapy without these drugs rarely causes severe cADR.
Asunto(s)
Antibacterianos/efectos adversos , Eritema Multiforme/inducido químicamente , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Inhibidores de la Bomba de Protones/efectos adversos , Síndrome de Stevens-Johnson/etiología , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Amoxicilina/efectos adversos , Claritromicina/efectos adversos , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Lansoprazol/efectos adversos , Masculino , Persona de Mediana Edad , Pirroles/efectos adversos , Rabeprazol/efectos adversos , Factores Sexuales , Sulfonamidas/efectos adversosRESUMEN
BACKGROUND: Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. AIMS: To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. METHODS: This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints. RESULTS: Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. CONCLUSIONS: Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).