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Molecular and Cellular Biochemistry Oct 2023Cyclophosphamide (CPA) is a classical chemotherapeutic drug widely used as an anticancer and immunosuppressive agent. However, it is frequently associated with...
Cyclophosphamide (CPA) is a classical chemotherapeutic drug widely used as an anticancer and immunosuppressive agent. However, it is frequently associated with significant toxicities to the normal cells of different organs, including the lung and heart. Lansoprazole (LPZ), a proton pump inhibitor (PPI), possesses antioxidant and anti-inflammatory properties. The current study investigated how LPZ protects against CPA-induced cardiac and pulmonary damage, focusing on PPARγ, Nrf2, HO-1, cytoglobin, PI3K/AKT, and NF-κB signaling. Animals were randomly assigned into four groups: normal control group (received vehicle), LPZ only group (Rats received LPZ at a dose of 50 mg/kg/day P.O. for 10 days), CPA group (CPA was administered (200 mg/kg) as a single i.p. injection on the 7th day), and cotreatment group (LPZ plus CPA). Histopathological and biochemical analyses were conducted. Our results revealed that LPZ treatment revoked CPA-induced heart and lung histopathological alterations. Also, LPZ potently mitigated CPA-induced cardiac and pulmonary oxidative stress through the activation of PPARγ, Nrf2/HO-1, cytoglobin, and PI3K/AKT signaling pathways. Also, LPZ effectively suppressed inflammatory response as evidenced by down-regulating the inflammatory strategic controller NF-κB, MPO, and pro-inflammatory cytokines. The present findings could provide a mechanistic basis for understanding LPZ's role in CPA-induced cardiopulmonary injury through the alleviation of oxidative stress and inflammatory burden.
Topics: Rats; Animals; Lansoprazole; NF-kappa B; NF-E2-Related Factor 2; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; PPAR gamma; Cytoglobin; Cyclophosphamide; Inflammation; Oxidative Stress; Oxidation-Reduction
PubMed: 36717473
DOI: 10.1007/s11010-023-04662-x -
The Yale Journal of Biology and Medicine 1999Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may... (Comparative Study)
Comparative Study Review
Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Clinical Trials as Topic; Enzyme Inhibitors; Esophagitis; Gastric Acid; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Lansoprazole; Omeprazole; Proton Pump Inhibitors; Proton-Translocating ATPases; Ranitidine
PubMed: 10780580
DOI: No ID Found -
International Journal of Pharmaceutics Jul 2020Lansoprazole (LPZ) is an acid pump inhibitor, which readily degrades upon acidic or basic conditions and under heating. We investigated here LPZ stability upon...
Lansoprazole (LPZ) is an acid pump inhibitor, which readily degrades upon acidic or basic conditions and under heating. We investigated here LPZ stability upon incorporation in particles made of cyclodextrin metal-organic frameworks (CD-MOFs). LPZ loaded CD-MOFs were successfully synthesized, reaching high LPZ payloads of 23.2 ± 2.1 wt%, which correspond to a molar ratio of 1:1 between LPZ and γ-CD. The homogeneity of LPZ loaded CD-MOFs in terms of component distribution was confirmed by elemental mapping by STEM-EDX. Both CTAB, the surfactant used in the CD-MOFs synthesis, and LPZ compete for their inclusion in the CD cavities. CTAB allowed obtaining regular cubic particles of around 5 µm with 15 wt% residual CTAB amounts. When LPZ was incorporated, the residual CTAB amount was less than 0.1 wt%, suggesting a higher affinity of LPZ for the CDs than CTAB. These findings were confirmed by molecular simulations. Vibrational circular dichroism studies confirmed the LPZ incorporation inside the CDs. Solid-state NMR showed that LPZ was located in the CDs and that it remained intact even after three years storage. Remarkably, the CD-MOFs matrix protected the drug upon thermal decomposition. This study highlights the interest of CD-MOFs for the incorporation and protection of LPZ.
Topics: Cetrimonium; Cyclodextrins; Drug Carriers; Drug Stability; Lansoprazole; Metal-Organic Frameworks; Microscopy, Electron, Transmission; Particle Size; X-Ray Diffraction; gamma-Cyclodextrins
PubMed: 32445910
DOI: 10.1016/j.ijpharm.2020.119442 -
BMJ (Clinical Research Ed.) Jan 2021To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms.
OBJECTIVE
To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms.
DESIGN
Pragmatic, double blind, placebo controlled, randomised trial.
SETTING
Eight ear, nose, and throat outpatient clinics, United Kingdom.
PARTICIPANTS
346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo.
INTERVENTION
Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks.
MAIN OUTCOME MEASURES
Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances.
RESULTS
Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups-score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval -0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (-0.6 to 5.4 points).
CONCLUSIONS
No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up.
TRIAL REGISTRATION
ISRCTN Registry ISRCTN38578686 and EudraCT 2013-004249-17.
Topics: Adult; Aged; Aged, 80 and over; Double-Blind Method; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Lansoprazole; Male; Middle Aged; Pharyngitis; Proton Pump Inhibitors; Quality of Life; United Kingdom
PubMed: 33414239
DOI: 10.1136/bmj.m4903 -
Gastroenterologie Clinique Et Biologique 2000
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Aged; Aged, 80 and over; Anti-Ulcer Agents; Female; Humans; Hyponatremia; Lansoprazole; Omeprazole
PubMed: 10962399
DOI: No ID Found -
British Journal of Clinical Pharmacology Mar 2017To evaluate the effect of lansoprazole, a proton-pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan-HER tyrosine kinase inhibitor, in... (Clinical Trial)
Clinical Trial
AIMS
To evaluate the effect of lansoprazole, a proton-pump inhibitor, on the absorption, pharmacokinetics, and safety of neratinib, a pan-HER tyrosine kinase inhibitor, in healthy subjects.
METHODS
This was an open-label, two-period, fixed-sequence study. Fifteen healthy adult subjects received a single oral dose of neratinib 240 mg (Period 1), followed by a washout period, then oral lansoprazole 30 mg once daily for 7 days and a single dose of neratinib 240 mg on Day 5 (Period 2). Pharmacokinetic sampling was performed for 72 h following each neratinib dose. Plasma neratinib concentration-time data were analysed using noncompartmental methods. Geometric mean ratios for AUC , AUC , and peak plasma concentrations (C ) for neratinib plus lansoprazole vs. neratinib were used to assess the magnitude of the drug-drug interaction if the 90% confidence intervals were outside 80.00-125.00%.
RESULTS
Neratinib geometric least-squares mean (LSM) C was reduced from 84.5 ng ml with neratinib alone to 24.5 ng ml with neratinib plus lansoprazole. The extent of exposure to neratinib was also decreased: geometric LSM AUC was 1478 ng ml h with neratinib vs. 426 ng ml h with neratinib plus lansoprazole, and geometric LSM AUC was 1557 ng ml h vs. 542 ng ml h, respectively. Mean t was similar with both treatments (approximately 14 h). Geometric mean ratios 90% confidence intervals for AUC , AUC and C fell outside the prespecified equivalence range (80.0-125.0%). Treatment-emergent adverse events, all mild, were reported by five (33%) subjects.
CONCLUSIONS
Coadministration of lansoprazole with neratinib reduced the rate and extent of neratinib exposure in healthy subjects.
Topics: Adult; Cross-Over Studies; Drug Interactions; Female; Healthy Volunteers; Humans; Lansoprazole; Male; Middle Aged; Protein Kinase Inhibitors; Proton Pump Inhibitors; Quinolines
PubMed: 27628584
DOI: 10.1111/bcp.13132 -
The Yale Journal of Biology and Medicine 1994Peripheral regulation of gastric acid secretion is initiated by the release of gastrin from the G cell. Gastrin then stimulates the cholecystokinin-B receptor on the... (Review)
Review
Peripheral regulation of gastric acid secretion is initiated by the release of gastrin from the G cell. Gastrin then stimulates the cholecystokinin-B receptor on the enterochromaffin-like cell beginning a calcium signaling cascade. An exocytotic release of histamine follows with concomitant activation of a C1- current. The released histamine begins the H2-receptor mediated sequence of events in the parietal cell, which results in activation of the gastric H+/K+ - ATPase. This enzyme is the final common pathway of acid secretion. The H+/K+ - ATPase is composed of two subunits: the larger alpha-subunit couples ion transport to hydrolysis of ATP, the smaller beta-subunit is required for appropriate assembly of the holoenzyme. Both the membrane and extracytoplasmic domain contain the ion transport pathway, and therefore, this region is the target for the antisecretory drugs of the post-H2 era. The 100 kDa alpha-subunit has probably 10 membrane spanning segments with, therefore, five extracytoplasmic loops. The 35 kDA beta-subunit has a single membrane spanning segment, and most of this protein is extracytoplasmic with the six or seven N glycosylation consensus sequences occupied. Omeprazole is an acid-accumulated, acid-activated, prodrug that binds covalently to two cysteine residues at positions 813 (or 822) and 892, accessible from the acidic face of the pump. Lansoprazole binds to cys321, 813 (or 822) and 892; pantoprazole binds to cys813 and 822. The common binding site for these drugs (cys813 or 822) is responsible for the inhibition of acid transport. Covalent inhibition of the acid pump improves control of acid secretion, but since the effective half life of the inhibition in man is about 48 hr, full inhibition of acid secretion, perhaps necessary for eradication of Helicobacter pylori in combination with a single antibiotic, will require prolongation of the effect of this class of drug.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amino Acid Sequence; Anti-Ulcer Agents; Enzyme Activation; Enzyme Inhibitors; Gastric Acid; Gastric Mucosa; H(+)-K(+)-Exchanging ATPase; Humans; Lansoprazole; Molecular Sequence Data; Omeprazole; Proton Pump Inhibitors; Stomach Ulcer
PubMed: 7502535
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2014Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may... (Meta-Analysis)
Meta-Analysis Review
Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. This review includes updated searches and new trials.Objectives To assess the effects of tranexamic acid versus no intervention, placebo or other antiulcer drugs for upper gastrointestinal bleeding.Search methods We updated the review by performing electronic database searches (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, Science Citation Index) and manual searches in July 2014.Selection criteriaRandomised controlled trials, irrespective of language or publication status.Data collection and analysis We used the standard methodological procedures of the The Cochrane Collaboration. All-cause mortality, bleeding and adverse events were the primary outcome measures. We performed fixed-effect and random-effects model meta-analyses and presented results as risk ratios (RRs) with 95% confidence intervals (CIs) and used I² as a measure of between-trial heterogeneity. We analysed tranexamic acid versus placebo or no intervention and tranexamic acid versus antiulcer drugs separately. To analyse sources of heterogeneity and robustness of the overall results, we performed subgroup, sensitivity and sequential analyses.Main results We included eight randomised controlled trials on tranexamic acid for upper gastrointestinal bleeding. Additionally, we identified one large ongoing pragmatic randomised controlled trial from which data are not yet available. Control groups were randomly assigned to placebo (seven trials) or no intervention (one trial). Two trials also included a control group randomly assigned to antiulcer drugs(lansoprazole or cimetidine). The included studies were published from 1973 to 2011. The number of participants randomly assigned ranged from 47 to 216 (median 204). All trials reported mortality. In total, 42 of 851 participants randomly assigned to tranexamic acid and 71 of 850 in the control group died (RR 0.60, 95% CI 0.42 to 0.87; P value 0.007; I² = 0%). The analysis was not confirmed when all participants in the intervention group with missing outcome data were included as treatment failures, or when the analysis was limited to trials with low risk of attrition bias. Rebleeding was diagnosed for 117 of 826 participants in the tranexamic acid group and for 146 of 825 participants in the control group (RR 0.80, 95% CI 0.64 to 1.00; P value 0.07; I² = 49%).We were able to evaluate the risk of serious adverse events on the basis of only four trials. Our analyses showed 'no evidence of a difference between tranexamic acid and control interventions regarding the risk of thromboembolic events.’ Tranexamic acid appeared to reduce the risk of surgery ina fixed-effect meta-analysis (RR 0.73, 95% CI 0.56 to 0.95), but this result was no longer statistically significant in a random-effects meta-analysis (RR 0.61, 95% CI 0.35 to 1.04; P value 0.07). No difference was apparent between tranexamic acid and placebo in the assessment of transfusion (RR 1.02, 95% CI 0.94 to 1.11; I² = 0%), and meta-analyses that compared tranexamic acid versus antiulcer drugs did not identify beneficial or detrimental effects of tranexamic acid for any of the outcomes assessed.Authors' conclusions This review found that tranexamic acid appears to have a beneficial effect on mortality, but a high dropout rate in some trials means that we cannot be sure of this until the findings of additional research are published. At the time of this update in 2014, one large study(8000 participants) is in progress, so this review will be much more informative in a few years. Further examination of tranexamic acid would require inclusion of high-quality randomised controlled trials. Timing of randomisation is essential to avoid attrition bias and to limit the number of withdrawals. Future trials may use a pragmatic design and should include all participants with suspected bleeding or with endoscopically verified bleeding, as well as a tranexamic placebo arm and co-administration of pump inhibitors and endoscopic therapy. Assessment of outcome measures in such studies should be clearly defined. Endoscopic examination with appropriate control of severe bleeding should be performed, as should endoscopic verification of clinically significant rebleeding. In addition, clinical measures of rebleeding should be included. Other important outcome measures include mortality (30-day or in-hospital), need for emergency surgery or blood transfusion and adverse events (major or minor).
Topics: Administration, Oral; Aluminum Hydroxide; Anti-Ulcer Agents; Antifibrinolytic Agents; Cimetidine; Drug Combinations; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage; Humans; Injections, Intravenous; Lansoprazole; Magnesium; Magnesium Hydroxide; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 25414987
DOI: 10.1002/14651858.CD006640.pub3 -
Alimentary Pharmacology & Therapeutics Jul 2000Omeprazole and lansoprazole can be given in sodium bicarbonate as, respectively, simplified omeprazole suspension and simplified lansoprazole suspension. We previously... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Omeprazole and lansoprazole can be given in sodium bicarbonate as, respectively, simplified omeprazole suspension and simplified lansoprazole suspension. We previously found the antisecretory effect of omeprazole 20 mg given as simplified omeprazole suspension to be lower than with intact capsules. However, lansoprazole 30 mg as simplified lansoprazole suspension produced an effect similar to that seen with intact capsules.
AIM
To evaluate the absorption of both drugs when given orally as capsules or as suspensions in sodium bicarbonate.
METHODS
In random order, we gave 5-day courses of omeprazole 20 mg and lansoprazole 30 mg as capsules and as suspensions in sodium bicarbonate to 12 healthy women. Serial blood samples were taken on days 1 and 5 of each course for pharmacokinetic measurements.
RESULTS
There was impairment of omeprazole absorption when given as simplified omeprazole suspension. Maximum plasma concentration and area under the concentration/time curve were lower with simplified omeprazole suspension than with omeprazole capsules (P=0.034 and 0.013, respectively, on day 5). No differences were found in lansoprazole absorption when simplified lansoprazole suspension was compared with its standard capsule formulation. Relative bioavailability of omeprazole from simplified omeprazole suspension compared to the capsule was 58.4% on day 5. The corresponding value for lansoprazole was 84.7%.
CONCLUSIONS
Simplified omeprazole suspension 20 mg does not supply adequate omeprazole for systemic absorption. Lansoprazole absorption from simplified lansoprazole suspension is maintained.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Absorption; Administration, Oral; Adult; Anti-Ulcer Agents; Area Under Curve; Capsules; Female; Humans; Lansoprazole; Omeprazole; Sodium Bicarbonate; Suspensions
PubMed: 10886044
DOI: 10.1046/j.1365-2036.2000.00794.x -
Lansoprazole fast disintegrating tablet: a new formulation for an established proton pump inhibitor.Digestion 2003Lansoprazole is a proton pump inhibitor (PPI) which is an effective and well-tolerated treatment option in the management of acid-related disorders. Lansoprazole fast... (Review)
Review
Lansoprazole is a proton pump inhibitor (PPI) which is an effective and well-tolerated treatment option in the management of acid-related disorders. Lansoprazole fast disintegrating tablet (LFDT)--a new, patient-friendly and more convenient formulation of lansoprazole which can be taken with or without water--is the first PPI to be made available as an orally disintegrating tablet. It represents an innovative drug delivery system, comprising enteric-coated microgranules of lansoprazole compressed with an inactive, rapidly dispersing matrix to form a tablet. When the tablet is placed on the tongue and sucked gently it disintegrates rapidly in the mouth, releasing the enteric-coated microgranules which are swallowed with the patient's saliva without water. Alternatively, the tablet can be swallowed with a drink of water. Studies have shown that the bioavailability of LFDT is comparable to lansoprazole capsules, at both 15 and 30 mg doses; the indications and recommended dosages for LFDT are therefore identical to lansoprazole capsules. The new formulation may be of particular benefit to those with active life-styles who do not always have water available, patients who have difficulty in swallowing, and elderly patients.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Anti-Ulcer Agents; Biological Availability; Chemistry, Pharmaceutical; Clinical Trials as Topic; Humans; Lansoprazole; Omeprazole; Peptic Ulcer; Proton Pump Inhibitors; Tablets
PubMed: 12743433
DOI: 10.1159/000070393