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Basic & Clinical Pharmacology &... Aug 2019
Topics: Cardiovascular Diseases; Cathepsin B; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Endothelium, Vascular; Humans; Lansoprazole; Omeprazole; Oxidative Stress; Proton Pump Inhibitors; Xanthine Dehydrogenase
PubMed: 30980783
DOI: 10.1111/bcpt.13237 -
Frontiers in Pharmacology 2021Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by... (Review)
Review
Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing eradication therapy. Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included. A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8-80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3-79.6%), 81.2% (1,498/1,844, 95% CI: 79.3-83.0%) and 86.8% (644/742, 95% CI: 83.9-88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06-1.39, = 0.006) and 1.57 (95% CI: 1.27-1.94, < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes ( < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar. The cure rates of PPI-amoxicillin-clarithromycin eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.
PubMed: 34721043
DOI: 10.3389/fphar.2021.759249 -
The Korean Journal of Internal Medicine Nov 2022Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly-used medications, and ailments such as arthritis or heart disease, require long-term use of these drugs,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly-used medications, and ailments such as arthritis or heart disease, require long-term use of these drugs, which can induce gastroenteropathy with bleeding and ulcers. This study investigated the associations between efficacy, safety, and gastrointestinal symptoms linked to rebamipide and proton pump inhibitor administration in patients requiring long-term NSAID use.
METHODS
This study was a multi-center, randomized, open-labeled, pilot design.
RESULTS
Thirty-three patients were included. Of these, 15 were included in the study group and 18 were in the control group. NSAID-induced gastric ulcers, which were the primary outcome of this study, did not occur in either the study or control group. Changes in the number of small bowel erosions and ulcers were -0.6 ± 3.06 in the study group and 1.33 ± 4.71 in the control group. The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) was three (20%) in the study group and six (40%) in the control group (p = 0.427). No serious adverse events occurred in either group. However, dyspepsia and skin rashes occurred in six patients (31.58%) in the study group and 13 (65%) in the control group (p = 0.036).
CONCLUSION
Although statistically significant differences were not generated, possibly as a result of the small sample size, mucosal breaks observed via capsule endoscopy revealed that rebamipide was likely to be more effective than lansoprazole in preventing small intestine damage caused by NSAIDs. Furthermore, fewer side-effects emerged with rebamipide.
Topics: Humans; Pilot Projects; Ulcer; Alanine; Intestinal Diseases; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 36375487
DOI: 10.3904/kjim.2021.216 -
Alimentary Pharmacology & Therapeutics Jan 2023Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tegoprazan is a novel potassium-competitive acid blocker used to treat acid-related disorders.
AIM
To compare tegoprazan 25 mg with lansoprazole 15 mg as maintenance therapy in healed erosive oesophagitis (EE) METHODS: In this phase 3, double-blind, multi-centre study, patients with endoscopically confirmed healed EE were randomised 1:1 to receive tegoprazan 25 mg or lansoprazole 15 mg once daily for up to 24 weeks. The primary efficacy endpoint was the endoscopic remission rate after 24 weeks. The secondary efficacy endpoint was the endoscopic remission rate after 12 weeks. Safety endpoints included adverse events, clinical laboratory results and serum gastrin and pepsinogen I/II levels.
RESULTS
We randomised patients to tegoprazan 25 mg (n = 174) or lansoprazole 15 mg (n = 177). Most had mild EE (Los Angeles (LA) grade A: 57.3%, LA grade B: 37.3%). The endoscopic remission rate after 24 weeks was 90.6% with tegoprazan and 89.5% with lansoprazole. Tegoprazan was not inferior to lansoprazole for maintaining endoscopic remission at 24 weeks and 12 weeks. In subgroup analysis, tegoprazan 25 mg showed no significant difference in maintenance rate according to LA grade (p = 0.47). The maintenance effect of tegoprazan was consistent in CYP2C19 extensive metabolisers (p = 0.76). Increases in serum gastrin were not higher in tegoprazan-treated than lansoprazole-treated patients.
CONCLUSIONS
Tegoprazan 25 mg was non-inferior to lansoprazole 15 mg in maintenance of healing of mild EE. In this study, tegoprazan had a similar safety profile to lansoprazole.
Topics: Humans; Lansoprazole; Gastrins
PubMed: 36314172
DOI: 10.1111/apt.17255 -
Scientific Reports Nov 2022The proton pump inhibitor lansoprazole has been previously identified to upregulate the expression and transcriptional activity of runt-related transcription factor 2...
The proton pump inhibitor lansoprazole has been previously identified to upregulate the expression and transcriptional activity of runt-related transcription factor 2 (Runx2) that promotes lineage commitment and differentiation of osteoprogenitor cells. We could not elicit the expected efficacy of insoluble lansoprazole in enhancing osteogenesis when combined with beta-tricalcium phosphate (β-TCP) bone substitutes. This study aimed to evaluate the effects of soluble lansoprazole on in vitro osteoblastogenesis and new bone formation in vivo. Commercially available human mesenchymal stem cells or patient-derived bone marrow-derived stromal cells were treated with 20 µM of soluble lansoprazole at the beginning of osteogenic induction. Soluble lansoprazole-impregnated β-TCP materials were embedded in the cortical bone defect model of rabbits. Rabbits were sacrificed four weeks postoperatively and undecalcified bone specimens were prepared for evaluation of intra-material new bone formation. Only a 1-day treatment with soluble lansoprazole facilitated osteoblastic differentiation and matrix calcium deposition when added to undifferentiated human mesenchymal stromal cells at the beginning of the osteogenic differentiation. Soluble lansoprazole dose-dependently accelerated intra-material new bone formation when being impregnated with porous β-TCP artificial bones. Local use of soluble lansoprazole can be applicable for fracture and bone defect repair when combined with porous β-TCP scaffolds.
Topics: Animals; Humans; Rabbits; Lansoprazole; Osteogenesis; Calcium Phosphates; Bone Regeneration; Lagomorpha
PubMed: 36446942
DOI: 10.1038/s41598-022-25184-4 -
Psychiatria Danubina Dec 2022Global warming is slowly but surely becoming one of the greatest problems of the modern world. Heatwaves with extremely high temperatures and humidity changes are... (Review)
Review
INTRODUCTION
Global warming is slowly but surely becoming one of the greatest problems of the modern world. Heatwaves with extremely high temperatures and humidity changes are particularly dangerous as they can lead to increased mortality rates and increased side effects of certain medications. The goal of this study was to give a short review of the most critical issues healthcare professionals should be mindful of when it comes to prescription of medicines during high temperature periods.
METHODS
A PubMed literature search was conducted in January 2021 in order to identify studies showing stability changes of most prescribed drugs in high temperatures as well as studies demonstrating impact of some drugs on human thermoregulation.
RESULTS
A vast majority of the commonly prescribed drugs, including Simvastatin, Levothyroxine, Omeprazole and Atorvastatin aren't susceptible to heat. However, some studies found that Amlodipine and Lansoprazole degrade following heat exposure. A study demonstrated the effects of low relative humidity environment on Levothyroxine tablets. While Levothyroxine remained stable at high temperatures, it significantly degraded with the decrease in humidity. Since all vaccines, both viral and bacterial, are most stable at exactly 2-8 °C, providing adequate storage has turned out to be an immense challenge. In general, killed whole-cell bacterial vaccines, like pertussis vaccine, show a higher degree of stability of potency compared to live attenuated vaccines, such as BCG. However, when tested in high-temperature conditions, BCG vaccine has proven to be more stable than Pertussis vaccine. Also, diphtheria and tetanus toxoids have proven to be most stable during exposure to various conditions. Many medicines can potentially have their side effects enhanced during heatwaves and cause serious health issues. Using the percutaneous form of nitroglycerin could lead to an additional decrease in blood pressure in warm weather. Subdermally injected insulin could create a severe hypoglycemia in diabetic patients. Studies have shown that schizophrenic patients on antipsychotic treatment have much lower heat tolerance, with a higher possibility of developing hyperthermic syndromes such as febrile catatonia or neuroleptic malignant syndrome.
CONCLUSION
Heatwave periods are not to be taken lightly and should be approached with utmost caution when prescribing therapy. It is of critical importance to inform and educate vulnerable populations early in the season and promote proper hydration throughout the periods when temperatures exceed local averages.
Topics: Humans; Global Warming; Thyroxine; Temperature; Pertussis Vaccine; Weather
PubMed: 36752238
DOI: No ID Found -
Metabolites Oct 2022Physiologically based pharmacokinetic (PBPK) modeling has a number of applications, including assessing drug−drug interactions (DDIs) in polymorphic populations, and...
Physiologically based pharmacokinetic (PBPK) modeling has a number of applications, including assessing drug−drug interactions (DDIs) in polymorphic populations, and should be iteratively refined as science progresses. The Simcyp Simulator is annually updated and version 21 included updates to hepatic and intestinal CYP2C19 enzyme abundance, including addition of intermediate and rapid metabolizer phenotypes and changes to the ultra-rapid metabolizer enzyme abundance, with implications for population clearance and DDI predictions. This work details verification of the updates with sensitive CYP2C19 substrates, omeprazole and lansoprazole, using available clinical data from literature. Multiple assessments were performed, including recovery of areas under the concentration-time curve (AUC) and Cmax from compiled datasets for each drug, recovery of victim DDI ratios with CYP2C19 and/or CYP3A4 inhibition and recovery of relative exposure between phenotypes. Simulated data were within respective acceptance criteria for >80% of omeprazole AUC values, >70% of lansoprazole AUC and Cmax, >60% of AUC and Cmax DDI ratios and >80% of exposure ratios between different phenotypes. Recovery of omeprazole Cmax was lower (>50−70% within 2-fold) and possibly attributed to the variety of formulations used in the clinical dataset. Overall, the results demonstrated that the updated data used to parameterize CYP2C19 phenotypes reasonably described the pharmacokinetics of omeprazole and lansoprazole in genotyped or phenotyped individuals.
PubMed: 36295903
DOI: 10.3390/metabo12101001 -
Pharmaceutics Dec 2021The current study aimed to design a novel combination of lansoprazole (LNS) and curcumin (CUR) solid oral dosage form using bioactive self-nanoemulsifying drug delivery...
BACKGROUND
The current study aimed to design a novel combination of lansoprazole (LNS) and curcumin (CUR) solid oral dosage form using bioactive self-nanoemulsifying drug delivery systems (Bio-SSNEDDS).
METHODS
Liquid SNEDDS were prepared using the lipid-excipients: Imwitor988 (cosurfactant), Kolliphor El (surfactant), the bioactive black seed (BSO) and/or zanthoxylum rhetsa seed oils (ZRO). Liquid SNEDDS were loaded with CUR and LNS, then solidified using commercially available (uncured) and processed (cured) Neusilin US2 (NUS2) adsorbent. A novel UHPLC method was validated to simultaneously quantify CUR and LNS in lipid-based formulations. The liquid SNEDDS were characterized in terms of self-emulsification, droplet size and zeta-potential measurements. The solidified SNEDDS were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), in vitro dissolution and stability in accelerated storage conditions.
RESULTS
Liquid SNEDDS containing BSO produced a transparent appearance and ultra-fine droplet size (14 nm) upon aqueous dilution. The solidified SNEDDS using cured and uncured NUS2 showed complete solidification with no particle agglomeration. DSC and XRD confirmed the conversion of crystalline CUR and LNS to the amorphous form in all solid SNEDDS samples. SEM images showed that CUR/LNS-SNEDDS were relatively spherical and regular in shape. The optimized solid SNEDDS showed higher percent of cumulative release as compared to the pure drugs. Curing NUS2 with 10% PVP led to significant enhancement of CUR and LNS dissolution efficiencies (up to 1.82- and 2.75-fold, respectively) compared to uncured NUS2-based solid SNEDDS. These findings could be attributed to the significant (50%) reduction in the micropore area% in cured NUS2 which reflects blocking very small pores allowing more space for the self-emulsification process to take place in the larger-size pores. Solid SNEDDS showed significant enhancement of liquid SNEDDS stability after 6 months storage in accelerated conditions.
CONCLUSIONS
The developed Bio-SSNEDDS of CUR and LNS using processed NUS2 could be used as a potential combination therapy to improve the treatment of peptic ulcers.
PubMed: 35056898
DOI: 10.3390/pharmaceutics14010002 -
Einstein (Sao Paulo, Brazil) 2022To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type...
Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study.
OBJECTIVE
To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type 1 diabetes.
METHODS
Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed.
RESULTS
Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported.
CONCLUSION
Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual β-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies.
REGISTRY OF CLINICAL TRIALS
(www.ctri.nic.in) under number REF/2021/03/041415 N.
Topics: Child; Humans; Insulin; Diabetes Mellitus, Type 1; Pilot Projects; Cholecalciferol; Lansoprazole; C-Peptide; Blood Glucose; Disease Progression
PubMed: 36449759
DOI: 10.31744/einstein_journal/2022AO0149 -
Nihon Ronen Igakkai Zasshi. Japanese... 2023Proton-pump inhibitors (PPIs) are widely used. However, reports of their adverse effects are increasing. Older patients are prone to developing hyponatremia due to...
AIM
Proton-pump inhibitors (PPIs) are widely used. However, reports of their adverse effects are increasing. Older patients are prone to developing hyponatremia due to various factors. The special environment of a geriatric healthcare facility tends to subject these patients to long-term medication use. Therefore, we hypothesized that nursing home residents receiving PPIs will present hyponatremia.
METHODS
The residents of Shonan Silver Garden, a long-term care health facility for older adults, were divided into two groups: a control group (n=61) which did not receive proton-pump inhibitors and a PPI group (n=29), which received proton-pump inhibitors for at least 6 months. The PPI group was further divided into the lansoprazole group (LPZ group) and the other PPI group. Other PPI users were excluded due to small numbers. The blood test results were compared between the control and LPZ groups. In the LPZ group, blood samples were taken 1 month after the discontinuation of lansoprazole, and serum Na level was compared to the level before discontinuation.
RESULTS
Blood Na levels in the PPI were lower than those in the control group, and hyponatremia (<136 mEq/L) was more frequent in the LPZ group than in the control group. There were no significant differences in other blood test parameters between the control and LPZ groups. At one month after the discontinuation of lansoprazole, serum Na levels were significantly increased; however, they remained lower than those in the control group.
CONCLUSION
A higher rate of hyponatremia was induced in older residents of long-term care facilities who took lansoprazole for >6 months in comparison to those who did not take lansoprazole.
Topics: Aged; Humans; Hyponatremia; Lansoprazole; Nursing Homes; Proton Pump Inhibitors
PubMed: 37225507
DOI: 10.3143/geriatrics.60.153