Influence Of Proton Pump Inhibitors Research Articles

Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non-valvular atrial fibrillation

BackgroundDabigatran is a direct thrombin inhibitor used to decrease the risk of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Its prodrug, dabigatran etexilate (DE) is often co-administrated with a proton pump inhibitor (PPI) because of its adverse effects on the gastrointestinal tract. Drug-drug interactions between DE and PPIs in daily clinical practice have not been fully elucidated. MethodsChanges in blood dabigatran concentration (DC) were investigated using the dilute thrombin time test in a randomized, open-label, two-period crossover study including 34 Japanese patients with NVAF receiving dabigatran therapy with or without PPI. ResultsThe average trough DC was significantly higher without PPI than with PPI (83 ± 42.3 vs. 55.5 ± 24.6 ng/mL, respectively; P < 0.001). Similarly, the average peak DC was significantly higher without PPI than with PPI (184.1 ± 107.7 vs. 124 ± 59.2 ng/mL, respectively; P = 0.0029). The average ratio of DC change at the trough and peak levels did not differ significantly among the three PPI types. ConclusionsPPI administration significantly decreased the trough and peak DCs in patients with NVAF. Therefore, when prescribing PPIs for patients with NVAF in a clinical setting, the possibility that the bioavailability of dabigatran may decrease should be considered.

Su1268 - The Influence of Proton Pump Inhibitors on Pancreatic Cancer Risk and Survival after Diagnosis

Su1268 - The Influence of Proton Pump Inhibitors on Pancreatic Cancer Risk and Survival after Diagnosis

Influence of Proton Pump Inhibitors on Mycophenolic Acid Pharmacokinetics in Patients With Renal Transplantation and the Relationship With Cytochrome 2C19 Gene Polymorphism

BackgroundMost patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation. Materials and MethodsA total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively. ResultsThe mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P < .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P < .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P < .05). However, no differences were found according to genotype distribution in all groups (P > .05). ConclusionPolymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

Influence of different proton pump inhibitors on the pharmacokinetics of voriconazole

This study aimed to determine the influence of proton pump inhibitors (PPIs) on the pharmacokinetics of voriconazole and to characterise potential drug–drug interactions (DDIs) between voriconazole and various PPIs (omeprazole, esomeprazole, lansoprazole and rabeprazole). Using adjusted physicochemical data and the pharmacokinetic (PK) parameters of voriconazole and PPIs, physiologically based pharmacokinetic (PBPK) models were built and were verified in healthy subjects using GastroPlusTM to predict the plasma concentration–time profiles of voriconazole and PPIs. These models were then used to assess potential DDIs for voriconazole when administered with PPIs. The results indicated the PBPK model-simulated plasma concentration–time profiles of both voriconazole and PPIs were consistent with the observed profiles. In addition, the DDI simulations suggested that the PK values of voriconazole increased to various degrees when combined with several PPIs. The area under the plasma concentration–time curve for the time of the simulation (AUC0–t) of voriconazole was increased by 39%, 18%, 12% and 1% when co-administered with omeprazole, esomeprazole, lansoprazole and rabeprazole, respectively. Omeprazole was the most potent CYP2C19 inhibitor tested, whereas rabeprazole had no influence on voriconazole (omeprazole > esomeprazole > lansoprazole > rabeprazole). However, in consideration of the therapeutic concentration range, dosage adjustment of voriconazole is unnecessary regardless of which PPI was co-administered.

The influence of proton pump inhibitors and other commonly used medication on the gut microbiota

ABSTRACTProton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.

Influences of proton pump inhibitor on Helicobacter pylori adherence to the gastrointestinal cell lines.

Helicobacter pylori is a carcinogenic bacterium that could induce P-glycoprotein expression in the human gastrointestinal tract. Bacterial adherence to the gastrointestinal cell lines could be influenced by the level of P-glycoprotein. This study aimed to determine the influence of proton pump inhibitors that exhibit an inhibitory effect on P-glycoprotein in gastrointestinal carcinoma cell lines, namely Caco-2 and LS174T, in relation to H. pylori adherence. Caco-2 and LS174T cells lines treated with omeprazole and esomeprazole were used in this study to assess the bacterial attachment of H. pylori within certain incubation periods. The presence of proton pump inhibitors increased the H. pylori adherence in a time-dependent manner in both Caco-2 and LS174T cell lines. The double inhibition of P-glycoprotein using proton pump inhibitor and P-glycoprotein inhibitor caused low P-glycoprotein expression in the cell lines, resulting in higher H. pylori adherence compared to the control cell lines. Proton pump inhibitors may alter P-glycoprotein expression in the gastrointestinal tract, and subsequently H. pylori adherence on the cell lines, and may contribute to resistance to drug therapy.

Influence of proton pump inhibitors and histamine H2 receptor antagonists on serum phosphorus level control by calcium carbonate in patients undergoing hemodialysis: a retrospective medical chart review.

BackgroundHyperphosphatemia is one of the common complications in patients undergoing hemodialysis. Although calcium carbonate (CaC) is often used to control serum inorganic phosphorus level in dialysis patients, co-administration of gastric acid reducers (ARs) may interfere with the phosphate binding effect of CaC. We performed a retrospective medical chart review to study whether ARs attenuate the hypophosphatemic effect of CaC in patients undergoing hemodialysis.MethodsOne hundred and eight chronic hemodialysis patients receiving either CaC alone or CaC concomitant with one of the ARs (proton pump inhibitors and histamine H2-receptor antagonists) were retrieved from the medical charts in Juntendo University Nerima Hospital. The patients were subdivided according to the interval between hemodialysis sessions (interdialysis interval of 48 or 72 h). A multivariate analysis was performed to identify clinical covariates associated with the variability of serum inorganic phosphorus levels. The study protocol was approved by the Institutional Review Board before the study was begun.ResultsAmong patients on hemodialysis with a 72-h interdialysis interval, the magnitude of increase in serum inorganic phosphorus concentration in patients receiving CaC and AR was significantly greater than in those receiving CaC alone. While a similar trend was observed among patients with a 48-h interdialysis interval, the difference did not reach a significant level. A multivariate regression analysis revealed that concomitant administration of ARs with CaC and a longer interdialysis interval (72 h) were significantly and independently associated with the magnitude of increase in serum phosphorus concentration between dialysis sessions. No significant differences in albumin-corrected serum calcium concentrations and incidence of pathological fractures were observed between patients receiving CaC alone and those receiving CaC with ARs.ConclusionsConcomitant use of ARs with CaC may attenuate the hypophosphatemic effect of CaC in patients undergoing chronic hemodialysis. When hemodialysis patients require prescription of ARs for the prevention of upper gastrointestinal mucosal diseases (such as peptic ulcer), it may be prudent to choose a phosphate binder other than CaC.

SAT-200 - Influence of Proton Pump Inhibitors and H2 Receptor Antagonists on Direct Acting Antiviral HCV Sustained Virologic Response

SAT-200 - Influence of Proton Pump Inhibitors and H2 Receptor Antagonists on Direct Acting Antiviral HCV Sustained Virologic Response

Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

Proton pump inhibitors for reflux therapy in infants: effectiveness determined by impedance pH monitoring

To evaluate the influence of proton pump inhibitors (PPI) in predominantly milk-fed infants with symptoms of GERD by 24-h pH-multichannel intraluminal impedance (24-h pH-MII). Ten infants (8 males and 2 females) with a mean gestational age of 39 weeks (28-40) were included. 24-h pH-MII was performed before prescription and during intake of PPI. Total acid exposure time, bolus exposure time (acidic/non-acidic/total) and the number of refluxes (acidic/non-acidic/total) were determined. Clinical symptoms were recorded and used to calculate the Reflux Symptom Index (RSI) and the Symptom Severity Index (SSI). There was a significant decrease in the number of acidic refluxes, total acid exposure and acidic bolus exposure time. However, this went along with a significant increase in non-acidic bolus exposure time. The total number of refluxes and the total bolus exposure time remained unchanged. Under PPI, a decrease of SSI and RSI for pain-related symptoms could be observed. For respiratory symptoms and vomiting however no significant changes could be demonstrated. Under PPI, an improvement of pain-related symptoms could be shown. The decrease of acid exposure went along with an increase of non-acidic refluxes resulting in almost constant total reflux numbers. This finding is interpreted as main reason for some persisting symptoms despite adequate PPI dosage. Concluding from our data PPI therapy should only be indicated in case of pain, but has no effect in case of vomiting or recurrent respiratory symptoms.

СONCOMITANT ADMINISTRATION OF CLOPIDOGREL AND PROTON PUMP INHIBITORS: ARE THERE ANY OPEN QUESTIONS LEFT TODAY?

Concomitant administration of clopidogrel and proton pump inhibitors (PPI), the possible influence of PPI on the effectiveness of clopidogrel often raises questions among practitioners. Massive antithrombotic therapy increases the risk of upper gastrointestinal tract lesions. Concomitant administration of these drugs is studied in a large number of trials. Results of the most significant of these trials are considered. Safety of concomitant administration of clopidogrel and PPI, its impact on long-term outcomes of cardiovascular diseases, and a choice of particular PPI are also discussed.

The influence of proton pump inhibitors on incidence of bacteremia after endoscopic ultrasonography guided fine needle aspiration

Objective To investigate whether preoperative proton pump inhibitor （PPI） would in- crease the risk of bacteremia after endoscopic uhrasonography guided fine needle aspiration （EUS-FNA）. Methods Dogs were randomly divided into experimental group （n = 8） to take 20mg of omeprazole orally twice a day for 3 days before EUS-ENA, and control group （ n = 10） to take placebo. EUS-FNA was performed to puncture the pancreas, and blood was collected before and after the procedure for culture. Bacteremia incidence of the two groups were compared. Results Bacteria culture was positive in 11 edogse. After excluding contamination, 1 dog in experimental group and 3 in control group were authentical bacteremia. There was no significant difference on the incidence of bacteremia between 2 groups based on Fisher test （ P = 0. 383 ）. Conclusion Aplication of PPI before EUS-FNA is not likely to increase the incidence of bacteremia. Key words: Endoscopic ultrasonography; Bacteremia; Micropunctures ; Proton pump inhibitor

Measurement of Mucosal Conductivity by MII Is a Potential Marker of Mucosal Integrity Restored in Infants on Acid‐suppression Therapy

Esophageal multichannel intraluminal impedance (MII) allows measurement of the conductivity of adjacent contents. During esophageal rest, raw impedance levels may represent mucosal integrity. We assessed the influence of proton pump inhibitors (PPIs) on presumed mucosal integrity by reanalyzing raw MII levels of 21 pH-MII tracings from infants with gastroesophageal reflux (GER) disease before and after esomeprazole treatment. Median (interquartile range) esophageal MII increased during treatment, 938 (652-1304) versus 1885 (1360-2183) Ohm, P < 0.0001. Patients with lower MII levels demonstrated a larger increase on therapy: Spearman r2 = 0.28, P = 0.014. No correlation with standard GER parameters was observed. In conclusion, PPI therapy increases MII levels in infants with symptomatic GER disease.

&lt;i&gt;CYP2C19&lt;/i&gt;遺伝子多型別にみたクロピドグレルの薬効に対する各PPIの影響

Recent studies carried out in Western countries have suggested a potential adverse interaction between clopidogrel and proton pump inhibitors (PPIs), which inhibit CYP2C19 activity. The purpose of this study was to examine the influence of individual PPIs and CYP2C19 polymorphism on the antiplatelet effect of clopidogrel in Japan. The platelet aggregations induced by 20 μmol/L ADP and CYP2C19 single nucleotide polymorphisms (*2 and *3) were determined in 118 patients on aspirin plus clopidogrel (75 mg/day) therapy. Twenty-five and 13 patients were treated with lansoprazole and rabeprazole, respectively. The platelet aggregation of extensive metabolizers (EM : *1/*1) treated with lansoprazole tended to be higher than those not given a PPI (21.5 % vs. 17.4 %, respectively, p=0.14). Lansoprazole was observed to have no effect on platelet aggregation in intermediate metabolizers (IM : *1/*2 and *1/*3) and poor metabolizers (PM : *2/*2, *2/*3, and *3/*3). Furthermore, platelet aggregation in IMs and PMs not given lansoprazole was significantly higher than that in EMs taking lansoprazole. Rabeprazole did not affect platelet aggregation in any genotype. These results suggest that the influence of PPIs on the antiplatelet effect of clopidogrel is minimal in Japanese patients.

Treatment with clopidogrel and proton pump inhibitors in combination: a review of emerging evidence

Proton pump inhibitors often are prescribed in combination with clopidogrel to decrease risk of gastrointestinal bleeding after acute coronary syndrome. Clopidogrel is a prodrug that has to be metabolized in the liver to generate the active metabolite. Both medications are metabolized largely by the CYP2C19 enzyme; therefore, concerns exist that a drug-drug interaction during concomitant treatment with clopidogrel and a proton pump inhibitor may result in reduction of platelet inhibition. We have reviewed observational and randomized control studies that have evaluated the potential influence of proton pump inhibitors on the platelet inhibitory effect of clopidogrel, along with cardiovascular outcomes. We also have summarized regulatory and academic guidelines for treatment of patients in which concomitant therapy with clopidogrel and proton pump inhibitors may be indicated. Confounding issues, including differential effects of individual proton pump inhibitors on the pharmacodynamics of clopidogrel and variation in clopidogrel metabolism mediated by CYP2C19 gene polymorphisms, also are discussed.

Influence of proton pump inhibitors on anticoagulation by warfarin: Comparison of rabeprazole and lansoprazole

Influence of proton pump inhibitors on anticoagulation by warfarin: Comparison of rabeprazole and lansoprazole

Influence of proton pump inhibitors on dexamethasone-induced gastric mucosal damage in rats

The present study was designed to compare the curative role of proton pump inhibitors, omeprazole, rabeprazole and lansoprazole against dexamethasone-induced ulcer model. Dexamethasone (5 mg/kg/day) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all rats. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 minutes prior to dexamethasone for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as estimation of myeloperoxidase, cortisol, alkaline phosphatase, malondialdehyde, endogenous anti-oxidants like superoxide dismutase, catalase and reduced glutathione. In dexamethasone induced ulcer model, omeprazole showed significant decrease in malondialdehyde, myeloperoxidase, alkaline phosphatase level and increase in superoxide dismutase, catalase and reduced glutathione level as compared to rabeprazole and lansoprazole. Omeprazole showed significant reduction in cortisol content where as rabeprazole and lansoprazole did not show significant changes as compared to control. The result indicates that omeprazole is the most effective and selective proton pump inhibitor in dexamethasone induced ulcer model as compared to rabeprazole and lansoprazole.

The Influence of Proton Pump Inhibitors on the Antiplatelet Potency of Clopidogrel Evaluated by 5 Different Platelet Function Tests

Proton pump inhibitors (PPIs) are metabolized by the cytochrome P450 enzyme system to a variable degree and may therefore interact with the metabolism of clopidogrel to its active form. The conflicting data on this potential interaction may be due to the use of different PPIs and platelet function tests in recent studies. We therefore evaluated the influence of different PPIs on the antiplatelet effect of clopidogrel by 5 platelet function tests in the same population. Adenosine diphosphate (ADP)-inducible platelet reactivity was assessed in 230 patients on dual antiplatelet therapy after angioplasty and stenting for cardiovascular disease by the light transmission aggregometry, VerifyNow P2Y12 assay, vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry, and Impact-R. ADP-inducible platelet reactivity showed no significant differences between patients without (n = 95, 41.3%) and with PPI therapy (n = 135, 58.7%) in each test system (all P > 0.05). Furthermore, we observed no significant differences of ADP-inducible platelet reactivity between patients without PPIs and patients with pantoprazole (n = 95, 70.4%), esomeprazole (n = 22, 16.3%), omeprazole (n = 9, 6.65%), or lansoprazole (n = 9, 6.65%) (all P > 0.3). High on-treatment residual ADP-inducible platelet reactivity occurred to a similar extent in patients without and with PPI therapy in each assay (all P > 0.05). In conclusion, concomitant treatment with PPIs did not attenuate the antiplatelet effect of clopidogrel in patients on dual antiplatelet therapy irrespective of the type of PPI and the used test system.

Proton Pump Inhibitors and Mucus Secretion

I have read with great interest the article by Sarosiek et al. [1] reporting a stimulatory effect of rabeprazole on esophageal mucin. The article describes a pharmacological property which may have a pivotal role in protecting the esophageal mucosa against gastro-esophageal reflux and which appears to be unique in comparison with other proton pump inhibitors (PPIs). As quoted by Sarosiek et al., if we take into consideration the influence of PPIs on gastric mucin, neither omeprazole nor lansoprazole were found to increase gastric mucus secretion in experimental studies. On the contrary, we already reported, in a double-blind placebo-controlled study, that, in humans, a 4-week treatment with omeprazole 20 mg significantly reduces the amount of total and neutral mucoproteins into the gastric juice, as well as the viscous and protective properties of gastric mucus as assessed by means of a ‘mucoprotective index’ [2]. Gastric mucus secretion reverts to normal only 2 weeks after the drug withdrawal. Similar results were observed with lansoprazole (Guslandi et al., unpublished data). Hence, the finding of a mucus-stimulating effect by rabeprazole suggests that this effect is unrelated to the inhibition of the gastric proton pump and may be due to its specific chemical structure. Similar discrepancies have been shown in our past studies with other acid-inhibiting agents, H2-receptor antagonists. While cimetidine and famotidine promote qualitative alterations in gastric mucus secretion, other H2-blockers such as ranitidine and nizatidine have no similar effects [3, 4]. The ability of rabeprazole to enhance gastric and esophageal mucus secretion represents an additional therapeutic effect of remarkable value in clinical practice.

Role of Proton Pump Inhibitors in Calcium Absorption, Bone Resorption, and Risk of Hip Fracture

Objective: To review the influence of proton pump inhibitors (PPIs) on calcium absorption, bone remodeling, and fracture risk. Data Sources: A search via MEDLINE (1966–April 2007) was performed using the search terms proton pump inhibitors, omeprazole, calcium absorption, calcium malabsorption, bone resorption, and fracture risk. Study Selection and Data Extraction: English-language literature, including abstracts, preclinical and clinical trials, and review articles, were identified from the data sources and reviewed. Data Synthesis: Data on the effect of PPIs on calcium absorption are conflicting; however, the majority of data indicate that PPIs decrease intestinal calcium absorption, which could negatively affect bone strength. In particular, calcium carbonate may be more difficult to absorb in an environment with elevated pH due to PPI use. Data on the role of PPIs in osteoclast function are also conflicting, with one human study indicating decreased bone resorption due to inhibition of osteoclast function and another human study indicating no association between PPIs and osteoclast function. The risk of fracture with PPI use was evaluated in 2 studies, and both studies found an increased risk of fracture of 14–44% after PPI use. Conclusions: PPI use may increase a patient's risk of fracture. Additional studies are needed before causality can be established.