RESUMEN
ABSTRACT: Proton-pump inhibitors (PPIs) are widely prescribed to decrease stomach acid and treat various acid-related Gastrointestinal tract (GIT) diseases. However, genetic variations, particularly in the CYP2C19 gene, affect PPIs metabolism and efficacy. Variants in CYP2C19 can result in different rates of PPI metabolism, influencing their effectiveness. Personalized medicine strategies, such as genotyping for CYP2C19, have the potential to enhance the effectiveness of PPI therapy and patient safety. This review aims to describe the relevance of CYP2C19 genetic profiling in the indian population, including normal function (e.g. CYP2C19*1, *11, *13, *15, *18, *28, and 38), decreased function (e.g., CYP2C19*9, *10, *16, *19, *25, and 26), loss of function (e.g., CYP2C19*2, *3, *4, *5, *6, *7, *8, *22, *24, *35, *36, and *37), and increased function (e.g., CYP2C19*17) variants. This review also examines the clinical pharmacogenomics implementation consortium (CPIC)-CYP2C19-PPI guidelines to highlight the importance of pharmacogenomics (PGx)-informed personalized PPI therapy for gastroesophageal reflux disease and peptic ulcer disease treatment. On average, each person in India possesses eight pharmacogenetic (PGx) variants that can be clinically significant, underscoring the need for preemptive testing. Implementing CYP2C19 genetic testing in India requires expanding laboratory capacity, increasing accessibility in primary care, increasing public awareness, collaboration between pharmacovigilance and PGx programs, investing in advanced sequencing technologies, data management systems, and integration with electronic health records and clinical decision support systems. Addressing challenges such as genetic diversity, socioeconomic factors, health-care access issues, and shortage of trained professionals is essential for implementation. Due to the lack of definitive country-specific policies and PGx guidelines from Indian drug regulatory agencies, guidelines from international consortia such as the Clinical Pharmacogenetics Implementation Consortium and drug labeling offer crucial foundational evidence. This evidence can be used to enhance patient outcomes and ensure the safe and effective use of PPIs in India.
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Citocromo P-450 CYP2C19 , Pruebas de Farmacogenómica , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Citocromo P-450 CYP2C19/genética , India , Medicina de Precisión , Guías de Práctica Clínica como AsuntoRESUMEN
Proton pump inhibitors (PPIs) are frequently overprescribed and maintained without clear indication, leading to significant clinical and economic consequences. Deprescribing, which involves discontinuing or reducing the dose of a medication, lacks clear guidelines for PPIs, despite various approaches being described. Gradual tapering of PPIs appears to be an effective strategy, especially when combined with non-pharmacological measures and multimodal interventions. Additionally, it is crucial to involve the patient in the discussion and ensure a post-tapering follow-up plan.
Les inhibiteurs de la pompe à protons (IPP) sont fréquemment surprescrits et maintenus sans justification précise, ce qui entraîne des impacts cliniques et économiques notables. La déprescription, qui consiste à arrêter ou réduire la dose d'un médicament, manque de directives claires pour les IPP, bien que diverses méthodes soient proposées. Le sevrage progressif des IPP semble être une stratégie efficace, surtout lorsqu'il est associé à des mesures non pharmacologiques et à des interventions multimodales. Il est également crucial d'impliquer le patient dans les discussions et de prévoir un plan de suivi postsevrage.
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Deprescripciones , Guías de Práctica Clínica como Asunto , Inhibidores de la Bomba de Protones , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Humanos , Prescripción Inadecuada/prevención & controlRESUMEN
OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection. DESIGN: Through searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly. RESULTS: The RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety. CONCLUSION: Compared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.
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Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Metaanálisis en Red , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. METHODS: In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. RESULTS: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). CONCLUSION: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Pirroles/uso terapéutico , Pirroles/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Femenino , Persona de Mediana Edad , Masculino , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Adulto , Resultado del Tratamiento , China , Anciano , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificaciónRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a severe postoperative complication in patients undergoing major surgery. Proton pump inhibitors (PPIs) are used preoperatively as prophylaxis for postoperative gastrointestinal bleeding. Whether preoperative PPI use is associated with an increased risk of postoperative AKI remains uncertain. METHODS: This retrospective cohort study used electronic medical records from the clinical data warehouse of Peking University First Hospital to screen all adult hospitalizations undergoing major surgery between 1 January 2018 and 31 December 2020. Exposure was preoperative PPI use, defined as PPI use within 7 days before major surgery. The primary outcome was postoperative AKI, defined as AKI occurring within 7 days after major surgery; secondary outcomes included in-hospital AKI and in-hospital mortality. RESULTS: A total of 21,533 patients were included in the study (mean [SD] age, 57.8 [15.0] years; 51.2% male), of which 944 (4.4%) were prescribed PPI within 7 days before major surgery (PPI users). Overall, 72 PPI users (7.6%) and 356 non-users (1.7%) developed postoperative AKI. After adjustment, preoperative PPI use was associated with an increased risk of postoperative AKI (adjusted OR, 1.47; 95% CI, 1.04-2.07) and in-hospital AKI (adjusted OR, 1.41; 95% CI, 1.03-1.94). Moreover, subgroup analyses showed that the risk of PPI on postoperative AKI was amplified by the concomitant use of non-steroidal anti-inflammatory drugs or diuretics. No significant difference was observed between preoperative PPI use and in-hospital mortality in the fully adjusted model (adjusted OR 1.63; 95% CI, 0.55-4.85). CONCLUSIONS: Preoperative PPI use was associated with an increased risk of AKI in patients undergoing major surgery. This risk may be enhanced by the concomitant use of other nephrotoxic drugs. Clinicians should weigh the pros and cons before initiating PPI prophylaxis.
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Lesión Renal Aguda , Mortalidad Hospitalaria , Complicaciones Posoperatorias , Inhibidores de la Bomba de Protones , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Factores de Riesgo , Cuidados Preoperatorios/métodos , China/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Numerous clinical concerns have been expressed regarding the potential worsening of cyclin-dependent kinase 4/6 inhibitor effects in breast cancer patients because of co-administration of proton pump inhibitors. Hence, this study evaluated the effects of proton pump inhibitors on the pharmacokinetics of palbociclib and ribociclib in terms of cytochrome P450 (CYP) 3A4 and P-glycoprotein involvement. METHODS: The effects of omeprazole and rabeprazole on drug metabolism and efflux of these drugs were investigated using molecular docking, metabolic stability assay in rat liver microsomes, human recombinant CYP3A4 (rCYP3A4) enzymes, and Caco-2 cell monolayers, and in vivo pharmacokinetics with omeprazole and rabeprazole in (5 and 10 mg/kg) 30 min and 7 days before orally dosing palbociclib and ribociclib (10 mg/kg). RESULTS: Omeprazole and rabeprazole inhibited CYP3A4 enzyme activity in rCYP3A4 baculosomes with a 50-60% inhibition at 30 µM. Additionally, both omeprazole and rabeprazole (10 µm) significantly reduced the P-glycoprotein-mediated drug efflux of palbociclib and ribociclib. The 7-day pretreatment of omeprazole at a dose of 10 mg/kg resulted in 24% and 26% reductions in palbociclib's mean maximum plasma concentration) Cmax and area under the plasma concentration-time curve (AUC0-24 h), respectively. Palbociclib's pharmacokinetics were not significantly altered by the pretreatment with rabeprazole; however, ribociclib pharmacokinetics exhibited an 83.94% increase in AUC0-24 h. CONCLUSION: The findings indicate that long-term treatment with therapeutic doses of both omeprazole and rabeprazole can alter the pharmacokinetics of palbociclib and ribociclib. The co-administration of rabeprazole may alter the pharmacokinetics of palbociclib and ribociclib via CYP enzyme and P-glycoprotein inhibition.
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Aminopiridinas , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Citocromo P-450 CYP3A , Interacciones Farmacológicas , Microsomas Hepáticos , Omeprazol , Piperazinas , Inhibidores de la Bomba de Protones , Purinas , Piridinas , Rabeprazol , Animales , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacocinética , Piperazinas/farmacocinética , Piperazinas/farmacología , Piperazinas/administración & dosificación , Humanos , Purinas/farmacocinética , Purinas/farmacología , Ratas , Piridinas/farmacocinética , Piridinas/farmacología , Piridinas/administración & dosificación , Rabeprazol/farmacología , Rabeprazol/administración & dosificación , Rabeprazol/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Omeprazol/farmacología , Omeprazol/farmacocinética , Omeprazol/administración & dosificación , Masculino , Células CACO-2 , Aminopiridinas/farmacocinética , Aminopiridinas/farmacología , Aminopiridinas/administración & dosificación , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Ratas Sprague-Dawley , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/administración & dosificación , Hígado/metabolismo , Hígado/efectos de los fármacos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismoRESUMEN
BACKGROUND: Proton pump inhibitors (PPIs), which inhibit gastric acid secretion, are frequently prescribed to patients with Parkinson's disease (PD). Levodopa, the gold-standard treatment for PD, demonstrates enhanced solubility in acidic environments. Although PPIs increase gastric pH and may affect levodopa absorption, the effect of concomitant PPI use on levodopa pharmacokinetics in patients with PD remains unknown. This study aimed to investigate the effect of the concomitant use of esomeprazole, a PPI, on the pharmacokinetics of levodopa and carbidopa and clinical symptoms in patients with PD. METHODS: We prospectively enrolled 40 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and clinical symptoms before and two weeks after the concomitant use of esomeprazole. RESULTS: The plasma concentrations of levodopa 30 min after concomitant oral administration of levodopa and esomeprazole were significantly lower (4.92 ± 4.10 µmol/L) than those without concomitant esomeprazole use (6.26 ± 3.75 µmol/L; p = 0.027). The plasma concentrations of carbidopa showed no significant differences with respect to concomitant esomeprazole use. Significant elevation was recorded in all subscores of the Movement Disorder Society-sponsored revision of the Unified Parkinson's disease Rating Scale scores after concomitant use of esomeprazole. No significant differences were observed between Helicobacter pylori-negative and Helicobacter pylori-positive patients. Non-elderly patients (age ≤ 70 years) tended to be more susceptible to the effect of esomeprazole on levodopa pharmacokinetics and clinical symptoms. CONCLUSIONS: The unnecessary use of PPIs should be avoided in patients with PD, especially in non-elderly patients, to improve absorption of levodopa.
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Antiparkinsonianos , Carbidopa , Interacciones Farmacológicas , Esomeprazol , Levodopa , Enfermedad de Parkinson , Inhibidores de la Bomba de Protones , Humanos , Levodopa/farmacocinética , Levodopa/administración & dosificación , Levodopa/sangre , Esomeprazol/administración & dosificación , Esomeprazol/farmacocinética , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/sangre , Masculino , Femenino , Anciano , Antiparkinsonianos/farmacocinética , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/sangre , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacocinética , Carbidopa/farmacocinética , Carbidopa/administración & dosificación , Estudios ProspectivosRESUMEN
Background: Helicobacter pylori (Hp) infection predisposes to malignant and non-malignant diseases warranting eradication. In Belgium, resistance rates for clarithromycin demonstrate regional variations making the use of standard triple therapy (STT) borderline acceptable. According to a recent Belgian survey, STT and bismuth-based quadruple therapy (BQT), are equally frequent prescribed as first line treatment for treatment naïve Hp positive patients. This study aims to evaluate the eradication rates (ER) of BQT versus STT. Methods: Multicentre, non-blinded randomized, prospective study comparing ER in treatment-naïve Hp positive patients. ER were compared by intention to treat (ITT) and per protocol (PP) analysis. Results: Overall 250 patients were included (STT 126, BQT 124). Seventeen patients were lost to follow-up (6,8%). No significant difference in ER between BQT and STT was observed in ITT (73% vs 68%, p= 0,54) neither in PP analysis (81% vs 75%, p= 0,33). Side effects and endoscopic findings were comparable between groups. Post-hoc analysis showed no differences according to gender or site allocation. Conclusion: The numerical advantage of BQT did not translate in a significant improvement of ER when compared with STT. These results question the cost-effectiveness of BQT, while confirming the suboptimal eradication rates on STT. A nationwide monitoring of resistance patterns, maximal investments in treatment adherence as well as a detailed follow-up of the changing treatment landscape are mandatory to continuously optimise Hp ER in Belgium.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Femenino , Masculino , Bélgica , Helicobacter pylori/efectos de los fármacos , Persona de Mediana Edad , Bismuto/uso terapéutico , Estudios Prospectivos , Antibacterianos/uso terapéutico , Adulto , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Anciano , Claritromicina/uso terapéutico , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Metronidazol/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. METHODS: A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. RESULTS: In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. CONCLUSION: The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.
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Amoxicilina , Antibacterianos , Bismuto , Claritromicina , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Metronidazol , Omeprazol , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Femenino , Masculino , Niño , Omeprazol/administración & dosificación , Omeprazol/uso terapéutico , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Amoxicilina/administración & dosificación , Claritromicina/administración & dosificación , Claritromicina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Bismuto/administración & dosificación , Bismuto/uso terapéutico , Adolescente , Resultado del Tratamiento , Esquema de Medicación , Preescolar , Pruebas Respiratorias , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Pirroles/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Helicobacter pylori/efectos de los fármacos , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Estudios Prospectivos , Resultado del Tratamiento , Adulto , AncianoRESUMEN
BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. METHODS: Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. RESULTS: Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. CONCLUSIONS: Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.
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Microbioma Gastrointestinal , Pirroles , Neoplasias Gástricas , Sulfonamidas , Animales , Pirroles/administración & dosificación , Pirroles/farmacología , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Ratones , Ratones Transgénicos , ARN Ribosómico 16S/genética , Modelos Animales de Enfermedad , Masculino , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Citocinas/metabolismoRESUMEN
BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy. MATERIALS AND METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment. TRIAL REGISTRATION: clinicaltrials.gov: NCT05901051.
Asunto(s)
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Masculino , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Femenino , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Helicobacter pylori/efectos de los fármacos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Resultado del Tratamiento , Anciano , Adulto , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Esquema de MedicaciónRESUMEN
BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.
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Antibacterianos , Bismuto , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Tetraciclina , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Tetraciclina/uso terapéutico , Tetraciclina/administración & dosificación , Tetraciclina/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Bismuto/uso terapéutico , Bismuto/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Adulto , Helicobacter pylori/efectos de los fármacos , Resultado del Tratamiento , China , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Esquema de Medicación , Esomeprazol/uso terapéutico , Esomeprazol/administración & dosificación , Anciano , Adulto Joven , Pruebas Respiratorias , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/diagnóstico , Persona de Mediana Edad , Masculino , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Femenino , Estudios Prospectivos , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , China/epidemiología , Quimioterapia Combinada/métodos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Resultado del Tratamiento , Adulto , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Anciano , Pueblos del Este de AsiaRESUMEN
Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.
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Lesión Renal Aguda , Cisplatino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Inhibidores de la Bomba de Protones , Humanos , Cisplatino/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/administración & dosificación , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/complicaciones , Estudios Prospectivos , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Factores de Riesgo , Antineoplásicos/efectos adversos , Anciano , IncidenciaRESUMEN
BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.
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Clopidogrel , Citocromo P-450 CYP2C19 , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Inhibidores de la Bomba de Protones , Humanos , Clopidogrel/uso terapéutico , Clopidogrel/efectos adversos , Clopidogrel/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Masculino , Femenino , Stents Liberadores de Fármacos/efectos adversos , Anciano , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Intervención Coronaria Percutánea/efectos adversos , Citocromo P-450 CYP2C19/genética , Resultado del Tratamiento , Sistema de Registros , Pueblos del Este de AsiaRESUMEN
PURPOSE: Gastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis. METHODS: This study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated. FINDINGS: The mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%. IMPLICATIONS: Multiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis. CLINICALTRIALS: gov identifier: NCT04967014.
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Estudios Cruzados , Preparaciones de Acción Retardada , Esomeprazol , Famotidina , Gastritis , Esomeprazol/administración & dosificación , Esomeprazol/farmacología , Humanos , Famotidina/administración & dosificación , Masculino , Adulto , Femenino , Adulto Joven , Gastritis/tratamiento farmacológico , República de Corea , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacología , Concentración de Iones de Hidrógeno , Voluntarios Sanos , Determinación de la Acidez Gástrica , Ácido Gástrico/metabolismo , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacología , Antiulcerosos/farmacocinéticaRESUMEN
OBJECTIVE: This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. RESULTS: Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. CONCLUSIONS: P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.
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Esofagitis Péptica , Inhibidores de la Bomba de Protones , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Esofagitis Péptica/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Proton pump inhibitors (PPIs) are widely used in cancer patients despite accumulating data showing that they can impact the efficacy of major anticancer drugs. This is particularly important with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs). RESULTS: Most TKIs require gastric acidity for their absorption and some retrospective series demonstrated that coprescription decreases the survival benefit of some TKI use (erlotinib, gefitinib and pazopanib). Relations between microbiota, the immune system, and the efficacy of immunotherapy are now obvious, just as modifications to gut flora after PPIs use are well-known. Many retrospective articles, including articles based on individual-participant data from randomized studies, demonstrated that patients treated with CPIs have a poorer outcome (overall survival, progression-free survival and response rate) when they received PPIs concomitantly, while there was no impact of such coprescription among patients in control arms, not treated with immunotherapies. Similar data were also observed in patients treated with palbociclib. CONCLUSION: For these interactions, it is very important to use the precautionary principle and warn patients and physicians about this. In patients who require acid suppression because of severe symptoms, using antacids or H2 blockers could be recommended.
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Neoplasias , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Interacciones Farmacológicas , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.