RESUMEN
BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, inhibits gastric acid secretion and attenuates the antiplatelet function of clopidogrel more potently than esomeprazole. We investigated whether alternate-day dosing of vonoprazan might avoid this interaction with clopidogrel while providing sufficient gastric acid inhibition. METHODS: Following 24 h of pH monitoring (control regimen), 12 healthy volunteers received three regimens (clopidogrel-only regimen: clopidogrel 75 mg daily [q.d.]; vonoprazan alternate-day regimen: vonoprazan 10 mg every other day [q.o.d.] + clopidogrel 75 mg q.d.; vonoprazan daily regimen: vonoprazan 10 mg q.d. + clopidogrel 75 mg q.d.) for 14 days in a randomized open-label crossover manner. Intragastric pH monitoring was performed for 24 h on day 13 in the clopidogrel-only and vonoprazan q.d. regimens and for 48 h on days 13 and 14 in the vonoprazan q.o.d. regimen. Serum gastrin and inhibition of platelet aggregation (IPA) were measured before the commencement of pH monitoring in each regimen. RESULTS: Twelve volunteers completed the study. Equivalent median IPA values in the q.o.d. and q.d. regimens were measured (21.8% and 25%, respectively) and were significantly lower than that with the clopidogrel-only regimen (40.8%). The median pH4 holding time ratio for the vonoprazan q.o.d. regimen (49.7%) was superior to that of the clopidogrel-only regimen (18.4%), but was significantly inferior to that of the vonoprazan q.d. regimen (77.0%; p < 0.01). CONCLUSION: Alternate-day administration of vonoprazan could not prevent the interaction between vonoprazan and clopidogrel, and acid inhibition was inferior to that with vonoprazan daily administration. Alternate-day administration of vonoprazan thus appears to be of questionable clinical utility.
Asunto(s)
Gastrinas , Inhibidores de la Bomba de Protones , Clopidogrel , Estudios Cruzados , Humanos , Concentración de Iones de Hidrógeno , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de la Bomba de Protones/farmacología , Pirroles , SulfonamidasRESUMEN
BACKGROUND: Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels. METHODS: Eleven healthy volunteers were subjected to 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75 mg alone, vonoprazan 10 mg alone, and vonoprazan 10 mg plus pirenzepine 75 mg administered in a randomized crossover fashion. RESULTS: Median pH 4 holding time ratios (range) achieved with pirenzepine 75 mg, vonoprazan 10 mg, and vonoprazan 10 mg plus pirenzepine 75 mg were 6.9% (2.4-32.8%), 88.4% (54.6-100%), and 84.2% (40.3-100%), respectively. Respective serum gastrin levels were 79 (75-210) pg/ml, 310 (110-870) pg/ml, and 170 (140-930) pg/ml. In cases with hypergastrinemia (gastrin ≥ 200 pg/ml) induced by vonoprazan 10 mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370 to 180 pg/ml (P = 0.028). CONCLUSION: Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.
Asunto(s)
Ácido Gástrico/metabolismo , Gastrinas/sangre , Pirenzepina/farmacología , Inhibidores de la Bomba de Protones/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Estudios Cruzados , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. METHODS: Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. RESULTS: High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143-0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. CONCLUSION: SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II-III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.
Asunto(s)
Quimioradioterapia/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Proteínas Nucleares/metabolismo , Anciano , Femenino , Humanos , Masculino , Pronóstico , Estudios RetrospectivosRESUMEN
Decreased trough level of infliximab (TLI) is associated with diminished efficacy in patients with Crohn disease (CD). We examined whether TLI at 14 weeks subsequent to the start of infliximab (IFX) treatment would impact long-term clinical course.Serum IFX levels and antibodies to IFX (ATI) at 14 and 54 weeks after IFX administration were measured in 12 patients with mild to moderate CD. We examined patient background, clinical severity, blood test values, and the relationship between ATI and TLI up to 108 weeks.We compared the group with TLIâ<â3âµg/mL at 14 weeks (TLI(14)â<â3 group) the group with TLIâ>â3âµg/mL (TLI(14) ≥ 3 group). Patients in the TLI(14) ≥ 3 group were significantly more likely to use immunomodulators before IFX treatment induction (Pâ=â.01). At 54 weeks, 2 cases of ATI production were observed in the TLI(14)â<â3 group, but no ATI production was observed in the TLI(14) ≥ 3 group. TLI in the TLI(14) ≥ 3 group at 54 weeks was significantly higher than in the TLI(14)â<â3 group (6.5âµg/mL vs 1.0âµg/mL; Pâ<â.01). Although CD activity index and serum albumin values in the TLI(14) ≥ 3 group at 14, 54, and 108 weeks significantly improved compared to baseline, these improvements were not observed in the TLI(14)â<â3 group. The remission maintenance rate at 108 weeks evaluated with the Kaplan-Meier method was significantly higher in the TLI(14) ≥ 3 group than the TLI(14)â<â3 group (100% vs 33.3%; Pâ=â.02).The TLI 14 weeks after IFX treatment in patients with CD affects long-term outcome.
Asunto(s)
Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Infliximab/uso terapéutico , Adolescente , Adulto , Anciano , Estudios de Cohortes , Enfermedad de Crohn/sangre , Progresión de la Enfermedad , Femenino , Fármacos Gastrointestinales/farmacocinética , Humanos , Infliximab/farmacocinética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Adulto JovenRESUMEN
PURPOSE: The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP). METHODS: We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger's clinical activity index (CAI) of ≤ 4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤ 1. RESULTS: FIT results were significantly correlated with all activity scores when the disease duration was < 4 years. When the disease duration was ≥ 4 years, FIT results were significantly correlated with the CAI and MES but not with UCEIS. When the disease duration was ≥ 5 years, FIT and CAI were significantly correlated, whereas FIT and MES or FIT and UCEIS did not show any correlation. When the duration was ≥ 4 years, PGE-MUM and CRP showed a significant correlation with CAI, MES, and UCEIS. Receiver operating characteristic curve analysis of biomarker data for predicting endoscopic remission showed that the accuracy of FIT was superior to that of PGE-MUM and CRP in the < 4-year group. CONCLUSIONS: FIT is an accurate biomarker reflecting the endoscopic score until 4 years in patients with UC. However, owing to the increased number of false negatives, the usefulness of FIT may decline after 4 years. Hence, evaluation of UC in combination with other biomarkers is recommended.
Asunto(s)
Colitis Ulcerosa , Biomarcadores , Colitis Ulcerosa/diagnóstico , Colonoscopía , Heces/química , Humanos , Mucosa Intestinal/química , Complejo de Antígeno L1 de Leucocito , Sangre Oculta , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Prostaglandin E-major urinary metabolite (PGE-MUM) may be a novel biomarker for evaluating disease activity in ulcerative colitis (UC). We compared its usefulness to that of the fecal immunochemical occult blood test (FIT). METHODS: PGE-MUM and FIT measurements were performed of 92 urinary and fecal samples obtained from 60 patients with UC. Endoscopic activity was determined by Mayo endoscopic subscore (eMayo) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. RESULTS: PGE-MUM levels and FIT results showed a significant correlation with respect to eMayo (P < 0.001 and P < 0.001, respectively), and there was a significant difference in PGE-MUM values between the groups below eMayo1 and above eMayo2 (P = 0.012). Both biomarkers were significantly correlated with the UCEIS score (P < 0.001 and P < 0.001, respectively), and the PGE-MUM values were significantly different between groups below UCEIS1 and above UCEIS2 (P = 0.012). PGE-MUM and FIT were significantly correlated with eMayo in the group with a disease duration < 5 years (P = 0.041 and P < 0.001, respectively). Although PGE-MUM and eMayo differed significantly between groups over 5 years (P = 0.012), FIT was not correlated with eMayo (P = 0.101). CONCLUSIONS: PGE-MUM is useful as a biomarker as FIT for evaluating the endoscopic activity, particularly in long-term affected patients with UC.
Asunto(s)
Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/orina , Sangre Oculta , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biomarcadores/sangre , Biomarcadores/orina , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Colonoscopía , Dinoprostona/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Albúmina Sérica/metabolismo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
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).
Asunto(s)
Antiácidos/administración & dosificación , Ácido Gástrico/metabolismo , Jugo Gástrico/efectos de los fármacos , Inhibidores de la Bomba de Protones/administración & dosificación , Pirroles/administración & dosificación , Rabeprazol/administración & dosificación , Sulfonamidas/administración & dosificación , Adolescente , Adulto , Antiácidos/efectos adversos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Jugo Gástrico/metabolismo , Voluntarios Sanos , Humanos , Concentración de Iones de Hidrógeno , Japón , Masculino , Polimorfismo Genético , Inhibidores de la Bomba de Protones/efectos adversos , Pirroles/efectos adversos , Rabeprazol/efectos adversos , Sulfonamidas/efectos adversos , Adulto JovenRESUMEN
BACKGROUNDS/AIMS: Vonoprazan (VPZ) is the first clinically available potassium competitive acid blocker. This class of agents provides faster and more potent acid inhibition than proton pump inhibitors. Most strains of Helicobacter pylori are sensitive to amoxicillin. We hypothesized that dual therapy with VPZ and amoxicillin would provide the sufficient eradication rate for H. pylori infection. To evaluate this, we compared the eradication rate by the dual VPZ/amoxicillin therapy with that by the standard triple VPZ/amoxicillin/clarithromycin therapy. METHODS: Non-inferiority of the eradication rate of H. pylori by the dual therapy with VPZ 20 mg twice daily (bid) and amoxicillin 500 mg 3 times daily (tid) for 1 week to that by the triple therapy with VPZ 20 mg bid, amoxicillin 750 mg bid and clarithromycin 200 mg bid for 1 week was retrospectively studied. Propensity score matching was performed to improve comparability between 2 regimen groups. Successful eradication was diagnosed using the [13C]-urea breath test at 1-2 months after the end of eradication therapy. RESULTS: The intention-to-treat analysis demonstrated that the eradication rate by the dual therapy (92.9%; 95% CI 82.7-98.0%, 52/56) was not inferior to that of the triple therapy (91.9%; 95% CI 80.4-97.0%, 51/56; OR 1.275, 95% CI 0.324-5.017%, p = 0.728). There were no statistically significant differences in incidences of adverse events between 2 regimens. CONCLUSION: VPZ-based dual therapy (VPZ 20 mg bid and amoxicillin 500 mg tid for 1 week) provides an acceptable eradication rate of H. pylori infection without the need for second antimicrobial agents, such as clarithromycin.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Pirroles , Estudios Retrospectivos , Sulfonamidas , Resultado del TratamientoRESUMEN
Crohn's disease is recognized to increase the risk of gastrointestinal malignances. Adenocarcinoma is the most common malignancy in these patients. Association between Crohn's disease and adenocarcinoma in the small intestine has already been established, however, the association between neuroendocrine tumor and Crohn's disease remains uncertain. We report a 39-year-old man with Crohn's disease, who was diagnosed with NET in the rectum. He had suffered from fever and anal pain due to the anal fistula and abscess. The disease state was considered to be resistant to medical treatment. He underwent total proctocolectomy, small bowel resection, anal fistula drainage with ileostomy. Postoperative histology revealed a neuroendocrine tumor in the rectum. His postoperative course was uneventful, and he followed a good course under treatment with infliximab and mercaptopurine hydrate. This case highlights the need of careful observation of resected specimens in light of the possibility of NET, especially those with anal disorders.
Asunto(s)
Enfermedad de Crohn/complicaciones , Tumores Neuroendocrinos/etiología , Neoplasias del Recto/etiología , Adulto , Colonoscopía , Humanos , Masculino , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Radiografía , Fístula Rectal/etiología , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Recto/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Abdominal compartment syndrome (ACS) is associated with mortality in patients with critical illness such as severe acute pancreatitis, but it remains unclear whether decompressive laparotomy for ACS can improve the prognosis of patients. CASE PRESENTATION: A woman in her 60s visited our hospital because of upper abdominal pain. On the basis of her laboratory data and abdominal contrast-enhanced computed tomography findings, acute gallstone pancreatitis was diagnosed. She underwent endoscopic sphincterotomy for the removal of the common bile duct stone. Then, a drainage tube was placed in the bile duct. However, on the 5th hospital day, her intra-abdominal pressure increased to 22 mmHg and renal dysfunction was observed, which led to the diagnosis of ACS. As intensive medical treatments did not improve her ACS, she underwent decompressive laparotomy on the 9th hospital day. Postoperatively, her laboratory data and intravesical pressure improved, and she was discharged from the hospital after abdominal closure, continuous drainage, and antibiotic therapy. CONCLUSION: As the effectiveness of decompressive laparotomy for ACS has not been established, this treatment indication remains controversial. Decompressive laparotomy is considered useful for the management of ACS, if it is performed at an appropriate time, as in the present case.
Asunto(s)
Descompresión Quirúrgica/métodos , Hipertensión Intraabdominal/cirugía , Laparotomía/métodos , Pancreatitis/cirugía , Humanos , Hipertensión Intraabdominal/diagnóstico por imagen , Hipertensión Intraabdominal/etiología , Pancreatitis/diagnóstico por imagenRESUMEN
BACKGROUND: Strong reactive oxygen species (ROS) suppression in cancer stem-like cell components in various solid tumors is associated with therapeutic resistance. In this study, we investigated the influence of CD44v8-10 expression on the overall survival of esophageal squamous cell carcinoma (E-SCC) patients after definitive chemoradiotherapy (dCRT) and on radio-sensitivities of E-SCC cell lines treated with or without sulfasalazine, a CD44v8-10-xCT-GSH axis inhibitor. METHODS: Seventy-three patients with E-SCC who received dCRT were examined retrospectively. CD44v8-10 expression was analyzed immunohistochemically using paraffin-blocked pre-dCRT biopsy specimens obtained by esophagoscopy and was expressed as a histo-score (H-score). The relationship between the H-score and overall survival was analyzed. From human E-SCC cell lines (T.T, T.Tn, or Kyse-3650), we collected CD44v8-10High and CD44v8-10Low subpopulations using a cell sorter. Water-soluble tetrazolium salt-8 (WST), glutathione-SH (GSH) and ROS assays were performed to compare the effect of sulfasalazine on the radio-sensitivities of these subpopulations in T.Tn and Kyse-3650. RESULTS: High CD44v8-10 expression was independently associated with poor prognosis in E-SCC patients treated with dCRT (hazard ratio = 2.906, 95% CI = 1.277-6.611, p = 0.011). In CD44v8-10High cells of each cell line, sulfasalazine decreased cellular GSH levels, resulting in increased radiation-induced ROS and reduced cell viability. In contrast, sulfasalazine had no significant effects in CD44v8-10Low cells. CONCLUSION: High CD44v8-10 expression was an independent prognostic factor in E-SCC patients treated with dCRT. CD44v8-10-xCT-GSH axis inhibition sensitized CD44v8-10High E-SCC cells to ROS-inducing treatments such as radiotherapy. Targeting CD44v8-10-xCT-GSH axis may improve the prognosis of post-dCRT E-SCC patients.
RESUMEN
BACKGROUND: An optimum Helicobacter pylori-eradication regimen for hemodialysis patients is yet to be established because of different pharmacokinetics of amoxicillin involved between hemodialysis patients and healthy subjects. We investigated to establish appropriate doses of amoxicillin for H. pylori infection eradication in hemodialysis patients. METHODS: Of 409 hemodialysis patients screened for H. pylori infection, 37 H. pylori-positive patients were randomized to different 1-week eradication regimens: esomeprazole 20 mg twice a day (b.i.d.) and clarithromycin 200 mg b.i.d., plus amoxicillin at either 750 mg b.i.d. (group A; conventional) or 250 mg b.i.d. (group B; experimental). Sixty-three patients with normal renal function received the conventional regimen (group C). Successful eradication was confirmed by urea breath testing. RESULTS: Eradication rates of group B (reduced amoxicillin-regimen) were 84.2% in intention-to-treat analysis and 88.9% in per-protocol analysis, which were similar with group A (77.8 and 77.8%) and group C (74.6 and 81.0%). However, the incidence of adverse events in group A was significantly higher than that in group C (22.2 vs. 5.1%, p = 0.027). CONCLUSIONS: In H. pylori-positive hemodialysis patients, amoxicillin at 250 mg b.i.d. may be an appropriate scheme for eradication with equivalent effects to the conventional therapy and safety effects for adverse events.
Asunto(s)
Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Diálisis Renal/efectos adversos , Anciano , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Pruebas Respiratorias , Claritromicina/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Esomeprazol/uso terapéutico , Femenino , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Japón/epidemiología , Levofloxacino/uso terapéutico , Masculino , Persona de Mediana Edad , Prevalencia , Resultado del TratamientoRESUMEN
BACKGROUND: Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H2RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. AIMS: The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. METHODS: Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. RESULTS: Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47-88%), 88% (76-93%), and 99% (95-100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29-100%), 100% (95-100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173-508), 323 (196-521), and 504 (400-812) pg/ml. CONCLUSION: Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.
Asunto(s)
Acetamidas/farmacología , Ácido Gástrico/metabolismo , Gastrinas/sangre , Antagonistas de los Receptores H2 de la Histamina/farmacología , Piperidinas/farmacología , Inhibidores de la Bomba de Protones/farmacología , Piridinas/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Acetamidas/administración & dosificación , Adolescente , Adulto , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Determinación de la Acidez Gástrica , Reflujo Gastroesofágico/tratamiento farmacológico , Voluntarios Sanos , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Humanos , Concentración de Iones de Hidrógeno , Masculino , Piperidinas/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificación , Piridinas/administración & dosificación , Pirroles/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto JovenRESUMEN
Drug-drug interaction between antiacid and antiplatelet agents has not been fully elucidated. Vonoprazan, a new potassium competitive acid blocker, has been available in Japan. CYP2C19 and CYP3A4 are involved in the metabolism of clopidogrel, prasugrel, esomeprazole, and vonoprazan. Using a P2Y12 assay, we compared the effects of vonoprazan and esomeprazole on the antiplatelet functions of clopidogrel or prasugrel in 31 healthy Japanese volunteers (14 CYP2C19 homo-extensive (homo-EMs), nine hetero-extensive (hetero-EMs), and eight poor metabolizers (PMs)). Vonoprazan decreased the median inhibition of platelet aggregation (IPA) values of clopidogrel and prasugrel more potently than esomeprazole (P < 0.001 for clopidogrel and P = 0.011 for prasugrel). The same tendencies were observed when stratified by CYP2C19 genotype groups (P = 0.004 in homo-EMs, 0.033 in hetero-EMs, and 0.043 in PMs). Vonoprazan attenuated the antiplatelet function of clopidogrel more potently than esomeprazole. Esomeprazole did not affect that of prasugrel irrespective of CYP2C19 genotype.
Asunto(s)
Plaquetas/efectos de los fármacos , Clopidogrel/uso terapéutico , Citocromo P-450 CYP2C19/genética , Esomeprazol/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Pirroles/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Pueblo Asiatico/genética , Interacciones Farmacológicas/genética , Femenino , Genotipo , Humanos , Masculino , Agregación Plaquetaria/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. AIM: To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. METHODS: We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a 13 C-urea breath test. RESULTS: Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. CONCLUSION: In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains.
Asunto(s)
Amoxicilina/administración & dosificación , Antibacterianos/administración & dosificación , Farmacorresistencia Bacteriana , Fluoroquinolonas/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Inhibidores de la Bomba de Protones/administración & dosificación , Rabeprazol/administración & dosificación , Adulto , Anciano , Antibacterianos/farmacología , Femenino , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Hospitales Universitarios , Humanos , Japón , Masculino , Metronidazol/farmacología , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75 mg in the morning alone, or with omeprazole 10 mg, esomeprazole 10 mg, lansoprazole 15 mg, or rabeprazole 10 mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4 h after the last clopidogrel dose on Day 7 of each regimen. IPA by clopidogrel with rabeprazole administered at lunchtime, approximately 4 h after clopidogrel, was also measured. Mean IPAs in those concomitantly receiving omeprazole, esomeprazole, lansoprazole or rabeprazole (47.2 ± 21.1%, 43.2 ± 20.2%, 46.4 ± 18.8%, and 47.3 ± 19.2%, respectively) were significantly decreased compared with those receiving clopidogrel alone (56.0%) (all ps < 0.001). This decrease was observed when PPIs were administered separately in the evening. However, IPA by clopidogrel with rabeprazole administered at lunchtime was 51.6%, which was markedly similar to that of clopidogrel alone (p = 0.114). All tested PPIs reduce the efficacy of clopidogrel when administered concomitantly. Our preliminary data suggest that administration of rabeprazole 4 h following clopidogrel may minimize potential drug-drug interactions.
Asunto(s)
Inhibidores de la Bomba de Protones/administración & dosificación , Ticlopidina/análogos & derivados , Adulto , Clopidogrel , Citocromo P-450 CYP2C19/genética , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Voluntarios Sanos , Humanos , Japón , Masculino , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de la Bomba de Protones/farmacología , Rabeprazol/administración & dosificación , Ticlopidina/administración & dosificación , Ticlopidina/farmacología , Factores de TiempoRESUMEN
BACKGROUND AND AIM: Spinal kyphotic deformity occasionally results in gastroesophageal reflux disease (GERD). The effects of acid reflux on the esophagus in kyphotic patients are unclear, however, and it is unknown whether acid reflux, endoscopic GERD, and reflux-related symptoms improve following surgical spinal correction in these patients. Herein, we investigated the characteristics of GERD in kyphotic patients and the improvement in GERD following surgical correction. METHODS: In 48 patients with severe kyphotic deformity scheduled for surgical spinal correction, we conducted esophagogastroduodenoscopy, 24-h pH monitoring and three questionnaire surveys, including the frequency scale for the symptoms of GERD (FSSG). We repeated these measurements after surgical correction and compared pre- and post-surgery values. RESULTS: Of 48 patients, 70.8% [95% CI: 55.9-83.0%, 34/48] had endoscopically evaluated esophageal mucosal injury. Regarding pH before surgery, 64.9% (CI: 47.5-79.8%, 24/37) had abnormal acid reflux (intraesophageal pH < 4 more than 5% of the time). FSSG score was significantly associated with the severity of GERD, and the positive rate was 52.6% (CI: 35.8-69.0%, 20/38). Following surgical correction, esophageal mucosal injury improved endoscopically in 90% of patients, and median total FSSG score significantly decreased from 8 (0-30) to 5 (0-19) (P = 0.005). Regarding pH after surgery, prevalence of abnormal acid reflux decreased from 66.7% (95% CI: 41.0-86.7%) to 33.3% (95% CI: 13.3-59.0%) (P = 0.045). CONCLUSION: Surgical spinal correction in kyphosis patients improves not only kyphotic deformity-related disorders but also esophageal mucosal injury, abnormal acid reflux, and reflux-related symptoms.
Asunto(s)
Reflujo Gastroesofágico/epidemiología , Cifosis/complicaciones , Osteotomía/métodos , Vértebras Torácicas/cirugía , Anciano , Progresión de la Enfermedad , Endoscopía del Sistema Digestivo , Monitorización del pH Esofágico , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/etiología , Reflujo Gastroesofágico/fisiopatología , Humanos , Incidencia , Japón/epidemiología , Cifosis/epidemiología , Cifosis/cirugía , Masculino , Periodo Posoperatorio , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND AND AIM: Healing speed of peptic ulcer is affected by a number of factors, including Helicobacter pylori (H. pylori) infection and intragastric pH. Acid inhibition exerted by proton pump inhibitors differs by CYP2C19 genotype. Herein, we investigated whether healing speed of artificial ulcers formed after endoscopic submucosal dissection (ESD) was influenced by H. pylori infection, CYP2C19 genotype, or other factors. METHODS: A total of 96 H. pylori-positive patients with gastric tumors scheduled for ESD were randomly assigned to receive eradication therapy for H. pylori before ESD (pre-ESD eradication) (n = 44) or after (post-ESD eradication) (n = 52). Patients received eradication therapy consisting of lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 mg twice daily for 1 week. After ESD, lansoprazole 30 mg was given once daily for 8 weeks. Ulcer size was endoscopically measured on the next day and at 4 and 8 weeks after ESD. RESULTS: Mean reduction rate of artificial ulcer area in the pre-ESD eradication group was 94.7% ± 5.5% at 4 weeks, which was similar to that in the post-ESD eradication group (94.7% ± 6.7%, P = 0.987), irrespective of CYP2C19 genotype. In multivariate analyses, location of gastric tumor (middle and upper, odds ratio: 4.05, 95% CI: 1.620-10.230, P = 0.003) was a factor for 97% reduction of artificial ulcer area at 4 weeks post-ESD, but CYP2C19 genotype and H. pylori infection were not. CONCLUSION: Healing speed of ESD-induced artificial ulcer was affected by tumor location, but not by time of H. pylori eradication, resected size, or CYP2C19 genotype.