Effects Of Famotidine Research Articles

Effectiveness of famotidine on the risk of poor prognosis in patients with COVID-19: A nationwide cohort study in Korea

ObjectiveFamotidine has been proposed as a promising candidate for the treatment of coronavirus disease 2019 (COVID-19). However, there is limited research on the association of famotidine with the poor prognosis of COVID-19. MethodsThe Korean nationwide cohort included 6,556 patients who tested positive on RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The poor COVID-19-related outcomes were defined on the basis of having encountered the composite outcome of high oxygen therapy, intensive care unit admission, administration of mechanical ventilation, or death. In addition, we performed exposure-driven propensity score matching for no H2-blocker use versus current famotidine use, and other H2-blocker use versus current famotidine use. Results4,785 (73.0%) patients did not use a H2-blocker, 393 (6.0%) patients were currently used famotidine, and 1,292 (19.7%) patients currently used H2-blocker other than famotidine. In multivariable analysis after matching (no H2-blocker use versus current famotidine use), there was no significant association between current famotidine use and composite outcomes (adjusted odd ratios [aOR]: 1.30, 95% confidence interval [CI]: 0.55–3.06). On the other hand, another matched cohort (other H2-blocker use versus current famotidine use), demonstrated a positive association between current famotidine use and composite outcomes (aOR: 3.56, 95% CI: 1.03–12.28) ConclusionsOur study results did not support the potential of famotidine as a therapeutic agent for COVID-19. A rather unexpected result could be observed in the comparisons between current famotidine use and other H2-blocker use; it was observed that current famotidine use increased the risk of poor COVID-19 related outcomes. Further studies are needed to clearly prove the causal relationship with several H2-blockers, including famotidine.

Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study

ObjectivesThis is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. MethodsA total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. ResultsAt weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. ConclusionOur study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. Trial registrationThis trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).

Effects of Famotidine on COVID-19 Patients in Intensive Care Unit: A Retrospective Clinical Trial

Effects of Famotidine on COVID-19 Patients in Intensive Care Unit: A Retrospective Clinical Trial

Therapeutic Status of Famotidine in COVID-19 Patients: A Review.

The novel coronavirus, SARS-coV-2, which emerged in Wuhan in November 2019, has increasingly spread worldwide. More than 272 million cases of infection have been identified. COVID-19 has affected 223 countries and territories across the world. The principal target of the SARS-CoV-2 infection is the lower respiratory tract. Series of moderate to non-specific severe clinical signs and symptoms appear two to fourteen days after exposure to SARS-CoV-2 in patients with COVID-19 disease, including cough, breath deficiency, and at least two of these symptoms: headache, fever, chills, repeated rigor, myalgia, oropharyngitis, anosmia, and ageusia. No therapeutic agents have been validated to have substantial efficacy in the clinical care of COVID-19 patients in large-scale trials, despite worsening infected rates of COVID-19. Early clinical evidence from many sources suggests that treatment with famotidine may decrease COVID-19-related morbidity and mortality. The mechanism by which famotidine could improve the outcomes of COVID-19 is currently unknown. A more recent postulated mechanism is that the effect of famotidine is mediated by histamine-2 receptor antagonism or inverse agonism, inferring that the SARS-CoV-2, resulting in COVID-19 infection, at least partially leads to the abnormal release of histamine and perhaps dysfunction of mast cells.

Effect of famotidine on hospitalized patients with COVID-19: A systematic review and meta-analysis.

IntroductionFamotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.MethodsFive databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.ResultsFour studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death—HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.ConclusionBased on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.

Radioprotective Effects of Combined Melatonin and Famotidine Treatment on Radiation Induced Apoptosis in Peripheral Blood Leukocytes of Breast Cancer Patients and Normal Individuals.

Objective The aim of this study was to evaluate the effects of individual or combined use of two antioxidants, melatonin and famotidine on radiation induced apoptosis in leukocytes from breast cancer (BC) patients. Materials and Methods In this experimental study, the DPPH assay was used to determine the appropriate doses of melatonin and famotidine for treatment of BC and control leukocytes. The leukocytes were cultured in complete RPMI- 1640 medium and treated with either agent for two hours. Cells were exposed to 4 Gy gamma rays generated from a Co-60 source at a dose rate of 0.85 Gy for 48 hours before harvesting. The cells were placed on slides and the neutral comet assay was performed. A total of 500 cells were stained with ethidium bromide and assessed for the amount of apoptosis under a fluorescent microscope x400 magnification. Results We observed significantly more apoptosis following radiation alone in the leukocytes from BC patients compared with normal individuals (P<0.01). Individual use of famotidine and melatonin induced very low frequencies of apoptosis that was not significantly different from the control (P>0.05). However, when combined with radiation, there was a decreased frequency of apoptosis in leukocytes of both normal and BC patients (P<0.05). The effect of famotidine was more pronounced than melatonin. ConclusionMelatonin, despite its potent antioxidant property, does not significantly affect radiation induced apoptosis in leukocytes derived from normal individuals; however, it has a moderately significant protective effect on in leukocytes derived from BC patients. Therefore, when used with radiation it might not intervene with the radiotherapy (RT) regimen of BC cancer patients. Famotidine is a good radioprotector for normal tissue. However, the efficacy of RT might be reduced with an accumulation of famotidine in tumour tissues.

Famotidine does not affect human sperm fertility characteristics (motility, viability and DNA integrity) in vitro.

Famotidine, a histamine-2 receptor antagonist, is commonly used to relieve the acid-related gastrointestinal diseases; however, its effect on human sperm parameters, and hence on sperm function, is still undetermined. Here, we intended to measure human sperm motility, viability, and DNA integrity of ejaculated human sperm in the presence of famotidine at 0, 0.1, 1 and 10mM concentrations in vitro. Forty-nine semen samples of normal count, motility, and morphology were included in this study. Sperm motility was assessed using Makler counting chamber and a phase contrast optics (200× magnification), whereas sperm viability was assessed using eosin-nigrosin staining procedure. The effect of famotidine on sperm DNA integrity was measured using flow cytometry. Famotidine at 0.1, 1 or 10mM had insignificant effect on human sperm motility (progressive, p=.9594; and total, p=.8420), sperm viability (p=.6471), and content of DNA breaks in sperm (p>.05) compared with the control. In conclusion, famotidine at 0.1, 1 or 10mM did not alter human sperm motility, viability or DNA integrity in vitro. Although, these findings indicate safety of famotidine in human sperm, further in vivo studies are required to establish the drug's safety.

Effect of famotidine in combination with antiepileptic drugs on locomotor activity in mice

Abstract Histamine type 2 receptor antagonists are one of the most commonly used agents to treat peptic ulcer disease. Since patients with epilepsy may have many comorbidities, the aim of this study was to investigate the influence of one of the strongest second generation histamine type 2 receptor antagonist, famotidine, on the exploratory and spontaneous activity in mice after 1 or 7 days treatment. Additionally, the interaction between famotidine and antiepileptics: carbamazepine, phenytoin, phenobarbital or valproate and their effect on animals activity was also evaluated. Locomotor activity was monitored electronically using a Digiscan analyzer in relation to ambulatory and rearing activities, as well as total distance travelled by animals during 15 minute periods. Results of our study indicate that famotidine administered alone did not modulate three variables of exploratory motor activity (horizontal activity, total distance and vertical activity) in mice. On the other hand, famotidine co-administered with valproate (1 day) or phenobarbital (1 day or 7 days) worsened vertical activity in mice in exploratory time. Similarly, impairment in horizontal activity in mice was observed when famotidine was given with phenobarbital (1 or 7 days). An increase in total distance in mice after famotidine alone or in combination with tested antiepileptic drugs was also shown. Moreover, famotidine alone or together with antiepileptic agents significantly impaired spontaneous locomotor activity in mice. The presented results show that famotidine administration to patients with epilepsy should be considered as potentially hazardous.

Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease.

BackgroundCardiac stem cells (CSCs) play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR) was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated.MethodsTo examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR) treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day) for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats.ResultsFunctional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment.DiscussionAs anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of healthy stem cell population is suggested as a possible mechanism underlying the cardioprotective effect of famotidine.

Histamine 2 receptor antagonism elicits protection against doxorubicin-induced cardiotoxicity in rodent model.

Doxorubicin (DOX), an anthracycline-based antibiotic, is regularly used in the management of carcinomas, and haematological malignancies have been downplayed in chemotherapy because of its ability to induce dilated cardiomyopathy (DCM). Dexrazoxane is approved to combat the cardiotoxicity, but limited by its adverse effects. Redox imbalance and reactive oxygen species generation plays major role in DOX-induced cardiotoxicity. Histamine, known to mediate various cardiovascular effects, but nevertheless the role of histamine or its receptors in DOX-induced DCM is remained obscure. Hence, this study is aimed to examine the effect of Famotidine (FAM), a H2 receptor antagonist on DOX-induced DCM in Wistar rats. Myocardial antioxidant status, stress and apoptosis markers, myocardial morphology and function were evaluated as the end points. Treatment with FAM has alleviated DOX doxorubicin-induced cardiotoxicity by reducing oxidative and nitrosative stress evident from lipid peroxidation and total nitrate-to-nitrite ratio, and enhanced the activity of super oxide dismutase. Cardiac stress markers like LDH and Na+-K+ATPase activities as well as CK-MB and Cardiac troponin levels were reduced by FAM treatment. It also normalised the myocardial function as assessed by 2D echocardiography and myocardial index. Treatment imparted anti-apoptotic effect as evident from decrease in myocardial caspase 3 and 9 activity and cleaved PARP expression. Effect of FAM is found to be comparable to the standard ACE inhibitor Captopril (CAP). The results from this study collectively suggest H2 receptor antagonism as a novel therapeutic strategy to impart biochemical, structural and functional improvement indicating its cardio-protective activity.

COMPARATIVE STUDY BETWEEN THE EFFECT OF HISTAMINE RECEPTOR ANTAGONISTS OF TYPE II (FAMOTIDINE) AND PROTON PUMP INHIBITORS (OMEPRAZOLE) ON THE EFFICACY OF CALCIUM CARBONATE AS PHOSPHATE BINDER IN HAEMODIALYSIS PATIENT

Objective: The purpose of this study was to compare the effect of famotidine versus omeprazole on the efficacy of calcium carbonate as a phosphate binder in the hemodialysis patient.Methods: From February 2014 to June 2014 a total number of 64 patients of both sexes were recruited from the department of renal dialysis, Tanta University Hospital, Egypt. Patients categorized into 3 groups. Group I (control group) consisted of 20 Patients (10) females and (10) males take calcium carbonate (caco3) (2.5–4 g/d) only, Group II consisted of 21 Patients (13) females and (8) males take the same dose of caco3 with famotidine 10 mg/d and Group III consisted of 23 Patients (8) females and (15) male take the same dose caco3 with omeprazole 20 mg/d.Results: All data are expressed as the mean±SD. Group II showed a significant increase (p&lt;0.05) in serum phosphorus at 3rd mo with significant decreased (p&lt;0.05) in serum calcium comparing with pre-treatment. Group III showed no significant change (p&gt;0.05) in serum calcium, phosphorus and parathyroid hormone (PTH) comparing with pre-treatment. Both groups (II and III) showed a significant decrease in alkaline phosphatase (ALP) (p&lt;0.05).Conclusion: Co-administration of famotidine with calcium carbonate aggravates hyperphosphatemia and this may increase the incidence of complications. The efficacy of calcium carbonate as a phosphate binder was not affected by co-administration of omeprazole.

Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers

PurposePreviously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. MethodsEffects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats. ResultsAliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model. ConclusionAliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.

Positive regulation of the enzymatic activity of gastric H+,K+-ATPase by sialylation of its β-subunit

The gastric proton pump (H+,K+-ATPase) consists of a catalytic α-subunit (αHK) and a glycosylated β-subunit (βHK). βHK glycosylation is essential for the apical trafficking and stability of αHK in gastric parietal cells. Here, we report the properties of sialic acids at the termini of the oligosaccharide chains of βHK. Sialylation of βHK was found in LLC-PK1 cells stably expressing αHK and βHK by staining of the cells with lectin-tagged fluorescent polymeric nanoparticles. This sialylation was also confirmed by biochemical studies using sialic acid-binding lectin beads and an anti-βHK antibody. The sialic acids of βHK are cleaved enzymatically by neuraminidase (sialidase) and nonenzymatically by an acidic solution (pH5). Interestingly, the enzymatic activity of H+,K+-ATPase was significantly decreased by cleavage of the sialic acids of βHK. In contrast, βHK was not sialylated in the gastric tubulovesicles prepared from the stomach of fed hogs. The H+,K+-ATPase activity in these tubulovesicles was not significantly altered by neuraminidase. Importantly, the sialylation of βHK was observed in the gastric samples prepared from the stomach of famotidine (a histamine H2 receptor antagonist)-treated rats, but not histamine (an acid secretagogue)-treated rats. The enzymatic activity of H+,K+-ATPase in the samples of the famotidine-treated rats was significantly higher than in the histamine-treated rats. The effects of famotidine were weakened by neuraminidase. These results indicate that βHK is sialylated at neutral or weakly acidic pH, but not at acidic pH, suggesting that the sialic acids of βHK positively regulate the enzymatic activity of αHK.

Comparison between the Protective Effects of Famotidine, Ginger and Marshmallow on Pyloric Ligation-Induced Peptic Ulcer in Rats

Background: Gastric ulcer is one of the most serious diseases over wide the world. There are many drugs used for the treatment of gastric ulcer, but most of these produce several adverse reactions. This study aims to investigate the protective effects of extracts of ginger and marshmallow on pyloric ligation-induced gastric ulcer in rats. Methods: Animals were divided into 5 Groups; a normal control group, an ulcer control group, a standard treatment group receiving famotidine (20 mg/kg), and two treatment groups receiving ginger (100 mg/kg) and marshmallow (100 mg/kg). Treatments were given orally for 14 days. On the 15th day, animals were subjected to pyloric ligation except for the normal control group. Four hours later, rat stomachs were excised and gastric juice and blood samples were collected. Results: Pyloric ligation caused significant elevations in ulcer number, ulcer index, gastric volume, titratble acidity, acid output, mucin content and peptic activity, accompanied by significant decreases in blood superoxide dismutase (SOD) activity and gastric mucosal nitric oxide (NO) and glutathione (GSH) contents. In addition, elevations in gastric mucosal lipid peroxide and histamine contents were observed. Pretreatment with famotidine, ginger or marshmallow significantly corrected all blood and tissue parameters by varying degrees. Conclusions: Famotidine, ginger and marshmallow may protect against pyloric ligation-induced peptic ulcer in rats, being promising for further clinical trials.

Effects of famotidine and vitamin C on low dose radiation-induced micronuclei in mice bone marrow cells

The radioprotective effects of vitamin C and famotidine were investigated using the micronucleus test for anticlastogenic and cell proliferation activity. Various doses of vitamin C and famotidine were administered intraperitoneally 2 h before 2Gy gamma irradiation to NMRI adult male mice. Frequency of micronuclei in 1000 PCEs (MnPCEs) were scored for each sample. Cell proliferation ratio (PCE/PCE+NCE) was also calculated. Data were statistically evaluated using one-way ANOVA and Tukey’s HSD test. The results indicated that gamma irradiation alone caused a significant increase in the MnPCEs and reduced the cell proliferation ratio. Administration of various doses of famotidine and vitamin C before gamma irradiation reduced MnPCEs and therefore clastogenic effects of radiation. Famotidine didn’t change cell proliferation compared to the irradiation group but vitamin C significantly improved and increased cell proliferation to the control group’s level. The dose reduction factor (DRF) calculated, shows a DRF=2 for famotidine and a DRF=1.7 for vitamin C which is indicative of a high radioprotective property of these compounds. The way in which these compounds reduced the clastogenic effects of radiation might be via antioxidant property and free radical scavenging mechanism.

Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

BackgroundApixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, and under development for treatment of venous thromboembolism. This study investigated the effect of a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist), on the pharmacokinetics of apixaban in healthy subjects.MethodsThis two-period, two-treatment crossover study randomized 18 healthy subjects to receive a single oral dose of apixaban 10 mg with and without a single oral dose of famotidine 40 mg administered 3 hours before dosing with apixaban. Plasma apixaban concentrations were measured up to 60 hours post-dose and pharmacokinetic parameters were calculated.ResultsFamotidine did not affect maximum apixaban plasma concentration (Cmax) or area under the plasma concentration-time curve from zero to infinite time (AUC∞). Point estimates for ratios of geometric means with and without famotidine were close to unity for Cmax (0.978) and AUC∞ (1.007), and 90% confidence intervals were entirely contained within the 80%–125% no-effect interval. Administration of apixaban alone and with famotidine was well tolerated.ConclusionFamotidine does not affect the pharmacokinetics of apixaban, consistent with the physicochemical properties of apixaban (lack of an ionizable group and pH-independent solubility). Apixaban pharmacokinetics would not be affected by an increase in gastrointestinal pH due to underlying conditions (eg, achlorhydria), or by gastrointestinal pH-mediated effects of other histamine H2-receptor antagonists, antacids, or proton pump inhibitors. Given that famotidine is also an inhibitor of the human organic cation transporter (hOCT), these results indicate that apixaban pharmacokinetics are not influenced by hOCT uptake transporter inhibitors. Overall, these results support that apixaban can be administered without regard to coadministration of gastric acid modifiers.

Effects of famotidine or an antacid preparation on the pharmacokinetics of nilotinib in healthy volunteers

This study evaluated the effects of either famotidine or antacid on the pharmacokinetics of nilotinib in healthy subjects, with the specific focus to explore different dosing separation schemes leading to a minimized drug-drug interaction. Fifty-two subjects were randomized to receive the following treatments in a crossover manner: (A) single oral nilotinib 400 mg alone; (B) famotidine 20 mg twice a day for 3 days, followed by a single administration of nilotinib 400 mg and famotidine 20 mg on Day 4, where famotidine was given 2 h after nilotinib; (C) single oral nilotinib 400 mg and antacid suspension 20 mL, where antacid was given 2 h before nilotinib; (D) single oral nilotinib 400 mg and antacid suspension 20 mL, where antacid was given 2 h after nilotinib. Comparing Treatment B to Treatment A, the geometric mean ratios of nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.966, 0.984, and 0.911, respectively (90% confidence intervals (CIs), 0.875-1.066, 0.905-1.069, and 0.798-1.039, respectively). Nilotinib pharmacokinetic parameters following Treatment C or Treatment D were similar to those after Treatment A; the corresponding 90% CIs of the geometric mean ratios of C(max), AUC(0-tlast), and AUC(0-inf) all fell within the bioequivalence range of 0.8-1.25. Neither famotidine nor antacid significantly affected nilotinib pharmacokinetics. When concurrent use of an H2 blocker or an antacid is necessary, the H2 blocker may be administered 10 h before and 2 h after nilotinib dose, or the antacid may be administered 2 h before or 2 h after nilotinib dose.

The beneficial effect of famotidine in patients with acute myocardial infarction

Objective: Survivors of myocardial infarction (MI) are at increased risk of cardiac remodeling and heart failure. Activated neurohormones, including histamine, play a critical role in this regard. Data from experimental animals indicated that blocking the activity of histamine served as a rational choice in treatment of this disease. The study was designed to evaluate the effect of famotidine in management of patients with acute MI. Method: The present study was a multicenter prospective randomized trial carried out at Al-Sader Teaching Hospital and Al-Fayhaa’ General Hospital, Basra, Iraq during the period from August 2010 to August 2011. Sixty patients were allocated into two groups. Group 1 (31 patients) received famotidine (40 mg/day) and group 2 (29 patients) received placebo formula in addition to the currently used drugs. All patients underwent initial echocardiographic evaluation at admission and 30 days after randomization along with measurement of N-terminal pro-brain natriuretic peptide (Nt-proBNP) levels. Results: Famotidine decreased the dilation of the left ventricle compared to placebo (P < 0.05), with an absolute decrease in left ventricular ejection fraction (P < 0.05). Famotidine treated patients also had a lower level of Nt-proBNP after completion of the study. Conclusion: Famotidine appears to have a beneficial role in management of patients who survive myocardial infarction.

Therapeutic effects of famotidine on chronic symptomatic gastritis: subgroup analysis from FUTURE study

A therapeutic strategy for symptomatic patients with chronic gastritis has not been established. Gastric acid has been reported to induce a variety of unpleasant abdominal symptoms. We investigated whether the histamine H2 receptor antagonist famotidine attenuated upper abdominal symptoms in patients with chronic gastritis. In this multicenter prospective single-arm open-label study, 10,311 patients with a clinical diagnosis of chronic symptomatic gastritis were enrolled and each patient was administered famotidine at 20 mg/day for 4 weeks. The intensity levels of upper abdominal symptoms, epigastralgia, epigastric fullness, and heartburn were evaluated using a face scale (grade 0-4). Abdominal symptom-related quality of life (QOL) impairment was also evaluated, using an Izumo scale before and after famotidine administration. In a subgroup analysis, symptomatic responses in patients diagnosed with functional dyspepsia (FD) according to the Rome III criteria were analyzed. In 8,460 patients who completed the protocol, famotidine administration significantly attenuated epigastralgia, epigastric fullness, and heartburn, and famotidine also attenuated abdominal symptom-related QOL impairment in all patients with chronic symptomatic gastritis, in those with FD-like symptoms without organic disease, and in those with FD as defined by the Rome III criteria. Famotidine is effective to relieve abdominal symptoms and improve QOL, not only in patients with Rome III-defined FD, but also in those with chronic symptomatic gastritis.

Influence of gastric acid on gastric emptying and gastric distension‐induced pain response in rats – effects of famotidine and mosapride

Gastroduodenal acidification has been reported to aggravate upper abdominal discomfort and pain that are symptoms suffered by functional dyspepsia (FD) patients. Delayed gastric emptying and hypersensitivity to gastric distension (GD) contribute importantly to the pathophysiology of FD. In the present study, we determined the influence of pentagastrin-stimulated endogenous gastric acid on gastric emptying and GD-induced pain responses using rat model systems. Moreover, we evaluated the effects of famotidine and mosapride on changes in gastric emptying and the GD-induced pain response to gastric acid hypersecretion. Gastric emptying was measured by excretion of glass beads that had been intragastrically administered with a liquid nutrient, and gastric pain response was evaluated by observing whether a GD-induced increase in mean blood pressure occurred. Pentagastrin (2 mg kg(-1), s.c.) which markedly and continuously stimulated gastric acid secretion, significantly delayed and enhanced respectively, gastric emptying and pain compared with saline-injected groups. Oral famotidine (0.1-3 mg kg(-1)) and mosapride (0.3-3 mg kg(-1)) administration in a dose-dependent manner accelerated the delay of gastric emptying. Furthermore, famotidine (0.3-3 mg kg(-1)) significantly alleviated the aggravation of the GD-induced pain response, but mosapride (10 mg kg(-1)) did not. We established rat models to evaluate the effect of gastric acid hypersecretion on gastric emptying and the GD-induced pain response. In these models, acid hypersecretion delayed gastric emptying and aggravated the pain response. Furthermore, we showed that famotidine ameliorated both delayed gastric emptying and gastric hypersensitivity, whereas mosapride only improved delayed gastric emptying.