Doses Of Famotidine Research Articles

Effects of esomeprazole on healing of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers in the presence of a continued NSAID treatment: Characterization of molecular mechanisms

Proton pump inhibitors promote ulcer repair in nonsteroidal anti-inflammatory drug (NSAID)-treated patients with ongoing NSAID-induced gastric toxicity, although the underlying mechanisms remain unclear. We examined the healing mechanisms of esomeprazole on NSAID-induced gastric ulcerations in the presence of a continued NSAID treatment. Ulcerations were induced in rats by oral indomethacin (6 μmol/kg/day) for 14 days. Indomethacin administration was continued, alone or combined with equivalent acid inhibitory doses of esomeprazole (5 μmol/kg/day), lansoprazole (15 μmol/kg/day) or famotidine (20 μmol/kg/day), for additional 7 days. Stomachs were then processed for: histomorphometric analysis of mucosal injury; mucosal levels of prostaglandin E 2 (PGE 2) and malondialdehyde (MDA); expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), caspase-3, and cyclooxygenase-2 (COX-2) (Western blot); expression of Ki-67 (immunohistochemistry). Indomethacin for 14 days elicited mucosal damage, reduced PGE 2 levels and increased MDA. After additional 7 days, indomethacin induced the following effects: further enhancement of mucosal damage and MDA content; decrease in PGE 2 levels; increase in COX-2 and activated caspase-3 expression; decrease in VEGF, PCNA and Ki-67 expression. In the presence of indomethacin, esomeprazole and lansoprazole were more effective than famotidine in promoting resolution of mucosal damage. Concomitantly, esomeprazole and lansoprazole, but not famotidine, restored PCNA and Ki-67 expression, and normalized MDA levels. Moreover, esomeprazole, lansoprazole and famotidine partly counteracted caspase-3 activation, without affecting VEGF expression. The healing activity of esomeprazole on indomethacin-induced gastric ulcerations can be ascribed to two mechanisms: (1) acid-dependent reduction of pro-apoptotic signalling; (2) acid-independent restoration of proliferating/repairing pathways.

Protective effect of roxatidine against indomethacin‐induced small intestinal mucosal injury in rats

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most significant causative factors of gastroduodenal ulcers. Recent reports have demonstrated that NSAIDs can also frequently induce ulceration and erosions of the small intestine. The aim of this study was to examine whether or not roxatidine (an H(2) receptor antagonist), which is known to increase gastric mucus in addition to inhibiting gastric acid, might suppress indomethacin-induced small intestinal mucosal injury, through an increase in mucus in rats. Rats were given two p.o. doses of roxatidine, famotidine or cimetidine before and after the s.c. indomethacin injection. The injured area of the small intestine was analyzed. To examine effects of drugs on small intestinal mucus, rats were also given two p.o. doses of roxatidine, famotidine or cimetidine, and the ratio of the periodic acid Schiff (PAS)-positive area to the area of the mucosa in the small intestine was analyzed. In addition, we evaluated the involvement of nitric oxide (NO) and prostaglandins (PG) in the effect of roxatidine on small intestinal mucus. Roxatidine significantly ameliorated indomethacin-induced small intestinal injury and increased the PAS-stained areas in the small intestinal mucosa, while cimetidine and famotidine had no significant effect. Pretreatment with N-nitro-L-arginine methyl ester but not with indomethacin, suppressed the effect of roxatidine on small intestinal mucus, suggesting that the effect is mediated by endogenous NO but not by PG. Roxatidine suppressed indomethacin-induced small intestinal injury in rats. One possible mechanism is an increase of small intestinal mucus, mediated by NO.

Effects of proton pump inhibitors on healing of gastric ulcerations induced by a continued non steroidal anti-inflammatory drug (NSAID) treatment

Proton pump inhibitors promote ulcer healing in NSAID-treated patients with ongoing NSAID-induced gastric toxicity. However, the underlying mechanisms are unknown. This study examined the molecular pathways contributing to healing actions of esomeprazole (ESO) and lansoprazole (LAN) on NSAID-induced gastric ulcers after a continued NSAID treatment. Ulcers were induced in male rats by daily oral indomethacin (IND, 6 μmol/kg) for 14 days. Animals were then treated with IND (6 μmol/kg), alone or in combination with equivalent acid inhibitory doses of ESO (5 μmol/kg), LAN (15 μmol/kg) or famotidine (FAM, 20 μmol/kg) for 7 days. Stomachs were processed for: 1) histomorphometric analysis of mucosal injury; 2) mucosal levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA); 3) expression of cyclooxygenase-2 (COX-2), VEGF and cleaved caspase-3 (Western blot); 4) expression of Ki-67 (immunohistochemistry). IND for 14 days induced mucosal damage (5.6±0.6%), reduced PGE2 mucosal levels (54.5±21.4 pg/mg) and increased MDA (8.4±1.0 nmol/mg). IND for additional 7 days enhanced further the mucosal damage and MDA, while PGE2 levels remained low. IND enhanced also the expression of COX-2 and caspase-3, reduced VEGF and Ki-67. In the presence of IND, treatment with ESO, LAN or FAM affected differentially most of the tested parameters. In particular: 1) ESO and LAN were more effective than FAM in reducing mucosal damage and MDA levels; 2) ESO and LAN, but not FAM, restored Ki-67 expression; 3) ESO, LAN and FAM partly counteracted IND-induced caspase-3 activation, without affecting the decrease in VEGF expression. The superiority of ESO and LAN over FAM in promoting ulcer healing in the presence of a continued IND treatment is likely to depend on both acid-dependent reduction of pro-apoptotic signalling and acid-independent restoration of repairing pathways.

Proton Pump Inhibitor-Induced Leak Across Gastric Mucosa: Effect of H-2 Blockers

Previous patient-based studies by our group have shown that the proton pump inhibitor, esomeprazole, induces a transmural leak in gastric mucosa (Mullin et al., Alimentary Pharmacology and Therapeutics, 28(11-12): 1317-25, 2008). Subsequent studies by our group using rat gastric corpus mucosa showed that this leak is bidirectional, has an upper size limit of 10 kDa, and is a class effect for PPIs in general, holding true for omeprazole and lansoprazole as well as esomeprazole. Additionally, we have demonstrated that the small molecule drug, digoxin, is capable of passing through this leak, with the potential of thereby elevating digoxin blood levels above their therapeutic target. In this current study we asked whether the H-2 blocker, famotidine, would have a similar effect to PPIs. Test subjects performed an initial (baseline) sucrose permeability test just prior to beginning medication. Subjects then took a daily (morning) dose of famotidine (40 mg) or omeprazole (20 mg) for 5 days. On the evening of the 5th (last) day, subjects performed a second sucrose permeability test. Subjects taking omeprazole for 5 days (n = 10) manifested a 5-fold increase in sucrose leak. Subjects taking famotidine for 5 days (n = 10) manifested only a 15% increase in leak, which was not statistically significant (P = 0.54, Student's t test). The increased leak of subjects on omeprazole was highly significant (P<0.0005). These findings support the hypothesis that induction of transmucosal gastric leak is not simply a function of inhibition of acid secretion, but instead is a property more specific to PPIs per se. Future studies will however test whether longer duration exposure to famotidine can induce leak, or whether a famotidine-induced leak disappears in 12-24 hrs after a 40 mg oral dose. This work was supported by funding from the Sharpe/Strumia Foundation.

Characterization of mechanisms underlying the effects of esomeprazole on the impairment of gastric ulcer healing with addition of NSAID treatment

The efficacy of proton pump inhibitors in patients at high risk of gastrointestinal injury receiving non-steroidal anti-inflammatory drugs is currently debated. To evaluate the effects of esomeprazole on the impairment of gastric ulcer healing associated with non-steroidal anti-inflammatory drug treatment. Gastric ulcers were induced in rats by acetic acid. Four days later, animals were treated daily with equivalent acid-inhibiting doses of esomeprazole or famotidine, alone or in combination with indomethacin. At day 3 or 7 of treatment, ulcerated tissues were processed to assess: ulcer area; malondialdehyde; prostaglandin E(2); nuclear factor-kB; proliferating cell nuclear antigen and caspase-3 (Western blot). In indomethacin-treated animals, esomeprazole was more effective than famotidine or the antioxidant melatonin in promoting ulcer healing. Malondialdehyde levels were increased by indomethacin, and this effect was counteracted by esomeprazole, but not famotidine. Esomeprazole and famotidine, given alone or in combination with indomethacin, increased proliferating cell nuclear antigen expression. Increased levels of prostaglandin E(2) were detected in ulcerated tissues. Ulcer prostaglandin E(2) production was reduced by indomethacin, alone or in combination with esomeprazole or famotidine, while it was enhanced when esomeprazole or famotidine were tested alone. The activation of caspase-3 was induced by indomethacin, and this effect was prevented by esomeprazole, but not famotidine. In the presence of indomethacin, esomeprazole, but not famotidine, enhanced nuclear factor-kB activation in gastric ulcers. Esomeprazole counteracts the detrimental action of indomethacin on ulcer repair through both acid-dependent and acid-independent effects. The acid-independent actions are related to decrease in tissue oxidation and apoptosis and to enhancement of nuclear factor-kB activation.

Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor

To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage. Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively. There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 +/- 3.49, and mean ulcer area; 21.00 +/- 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 +/- 2.47, P > 0.05), 20 mg/kg (2.37 +/- 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 +/- 3.06), and vardenafil 10 mg/kg (1.25 +/- 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 +/- 2.97, P < 0.001) , famotidine 20 mg/kg (0.94 +/- 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 +/- 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 +/- 0.88, P < 0.001) compared to the indomethacin group. MDA levels were significantly higher in indomethacin group (28.48 +/- 14.51), compared to the famotidine 5 mg/kg (6,21 +/- 1.88, P < 0.05), famotidine 20 mg/kg (5.88 +/- 1.60. P < 0.05), vardenafil 2 mg/kg (15.87 +/- 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 +/- 4.50, P < 0.05). NO concentration in gastric tissues of the famotidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed diminished gastric damage for pretreatment groups compared to the indomethacin group (P < 0.05). Vardenafil affords a significant dose-dependent protection against indomethacin induced gastric mucosal lesions in rats.

Effect of single oral dose of Famotidine administered a night before surgery on the intragastric pH and volume in adult patients undergoing elective surgery; a triple blind placebo controlled clinical trial

Objectives: To evaluate the effect of preanaesthetic administration of oral Nizatidine on pH and volume of gastric contents excluding samples contaminated with duodenogastric reflux.Design: Prospective, triple blind, randomized and placebo controlled clinical trial.Methods: The patients in Group C (Control) received Placebo while Group N (Nizatidine 300 mg) orally at 9.00 p.m., a night before elective surgery. Next day, gastric contents were aspirated with a large bore, multi-orifices gastric tube passed through an endotracheal tube placed blindly in esophagus after tracheal intubation and analyzed for the presence of bile salts, pH and volume.Results: Thirty five samples (29.66 %) out of 118 were contaminated with duodenal contents. One sample was contaminated with blood while one patient has no gastric contents. Duodenogastric reflux significantly affected pH and volume. Nizatidine, after excluding those samples contaminated either with duodenal fluid or blood, did not decrease significantly pH (p 0.0554), volume (p 0.5202) and the proportion of the patients (28.57% versus 24.39%) considered” at risk” compared with Placebo (p 0.8044) according to the criteria defined (pH ≤ 2.5 and volume ≥ 25 ml).Conclusion: Nizatidine 300 mg given orally, a night before surgery did not afford adequate prophylaxis for the acid aspiration syndrome excluding those samples contaminated with duodenogastric reflux.

Nursing Care of Patients Receiving High-Dose, Continuous-Infusion Interleukin-2 With Pulse Dose and Famotidine

High-dose, continuous-infusion interleukin-2 (IL-2) followed by pulse dose and concurrent administration of famotidine has demonstrated response rates of 64% and 33% in patients with metastatic melanoma and metastatic renal cell carcinoma, respectively. Currently, no information is available concerning the nursing care of patients receiving that IL-2 regimen. Given the high response rates of patients on the treatment, attention by the nursing profession is warranted. Effective nursing care of patients receiving IL-2 is essential to the regimen's success. Recognition and prompt treatment of common side effects lead to better patient outcomes. This article provides nurses with an overview of the treatment regimen, expected side effects, psycho-social considerations, and discharge instructions for patients receiving continuous-infusion plus pulse IL-2 and famotidine.

Effect of famotidine and lansoprazole on serum phosphorus levels in hemodialysis patients on calcium carbonate therapy

Histamine H2 receptor antagonists (HRA) or proton pump inhibitors (PPI) are frequently administered to patients on hemodialysis, because their intestinal mucosa is fragile. Although three studies have indicated that concomitant HRA administration causes a decrease in the binding of phosphate by calcium carbonate, the HRA doses tested in these studies were 2-4 times higher than the recommended dose for hemodialysis patients. In addition, it remains unclear whether PPI therapy affects serum phosphate levels in hemodialysis patients taking calcium carbonate. Accordingly, the aim of this study was to evaluate the influence of lansoprazole and the recommended dose of famotidine on serum phosphate and calcium levels in hemodialysis patients. The study included 115 hemodialysis patients who were taking calcium carbonate and who were also treated with either famotidine (10 mg/day) or lansoprazole (30 mg/day). Changes of the mean serum phosphate and calcium levels over 2 months before and after the start of famotidine or lansoprazole therapy were compared. The same parameters were also compared when famotidine was switched to lansoprazole. The mean serum phosphate level increased significantly after administration of either famotidine or lansoprazole (by 6.6 +/- 21.9% or 13.0 +/- 26.3%, p = 0.032 and p = 0.029, respectively). The mean serum calcium level was unchanged after administration of famotidine, but showed a significant decrease after administration of lansoprazole (by 3.44 +/- 7.73%, p = 0.013). Therefore, the calcium x phosphorus product was significantly increased by administration of famotidine, but not by administration of lansoprazole (6.68 +/- 23.37% and 8.73 +/- 27.41%, p = 0.046 and p = 0.251, respectively). When famotidine was switched to lansoprazole, the serum phosophate level did not change, but serum calcium decreased significantly by 3.8 +/- 13.0% (p = 0.0006). Not only administration of 20 mg/ day of famotidine as previously reported, but also 10 mg/day of this drug (the recommended dose for hemodialysis patients) caused a significant increase of serum phosphate in patients taking calcium carbonate. PPIs have been reported to show no effect on the serum phosphate level, but 30 mg/day of lansoprazole also caused a significant increase of serum phosphate in patients taking calcium carbonate.

Gastric Antisecretory Drugs Induce Leukocyte-Endothelial Cell Interactions through Gastrin Release and Activation of CCK-2 Receptors

Antisecretory drugs are effective antiulcer agents, but its chronic use generates hypergastrinemia and accelerates the development of atrophic gastritis in Helicobacter pylori-positive patients. We have recently shown that gastrin exerts a proinflammatory effect in rats through CCK-2 receptor activation that contributes to the inflammation induced by H. pylori. The present study was designed to examine whether gastrin hypersecretion in response to treatment with antisecretory drugs induces an inflammatory response that could promote mucosal atrophy. The effects of omeprazole or famotidine on leukocyte/endothelial cell interactions in vivo were analyzed in rat mesenteric venules using intravital microscopy. Administration of a single dose of omeprazole or famotidine acutely increased gastrinemia and leukocyte rolling and adhesion, but not emigration into the interstitium. Daily treatment with omeprazole for a short period (3 days) induced a similar response, but when this treatment was extended to 14 days and a steady hyper-gastrinemic state was established, increased leukocyte rolling, adhesion, and emigration was observed. Pretreatment with the CCK-2 receptor antagonist proglumide prevented these inflammatory events in all cases. Leukocytes from rats treated with omeprazole showed increased expression of CD11b/CD18 initially in granulocytes (3-day protocol) and later in monocytes and lymphocytes (14-day protocol). These changes were not observed in animals pretreated with proglumide, and they were not reproduced by incubation of leukocytes from untreated animals in vitro with gastrin. Thus, hypergastrinemia induced by chronic treatment with antisecretory drugs may promote inflammation, which could partly explain their worsening effect in corpus gastritis observed in H. pylori-infected patients.

Snapshots for July 2007

Snapshots for July 2007

Novel role of famotidine in downregulation of matrix metalloproteinase-9 during protection of ethanol-induced acute gastric ulcer

Gastric ulcer is a multifaceted process including acid secretion, reactive oxygen species generation, prostaglandin inhibition, and extracellular matrix (ECM) degradation. Matrix metalloproteinases (MMPs) have the ability to cleave and remodel the ECM. We investigated the activity and expression of MMP-9 and -2 in ethanol-induced acute gastric ulceration in rats. We found that severity of gastric ulcer was strongly correlated with increasing doses of ethanol and increased secretion of proMMP-9. ProMMP-9 was upregulated ∼25-fold at maximum ulcer index. Increased secretion of proMMP-9 was associated with increased expression of tumor necrosis factor-α and interleukin-6. We examined the effect of H 2-receptor antagonists and antioxidants on proMMP-9 secretion and synthesis during prevention of ethanol-induced gastric ulcer. Our data reveal that famotidine dose dependently blocked increased secretion and synthesis of proMMP-9 during gastroprotection and arrested infiltration of inflammatory cells as well as oxidative stress in rat gastric tissues. Similar to H 2-receptor antagonists, N-acetylcysteine and dimethyl sulfoxide, well-known antioxidants, inhibited proMMP-9 upregulation to the control level. In conclusion, ethanol-induced gastric ulceration is associated with increased expression of proMMP-9 that can be attenuated by H 2-receptor antagonists and antioxidants. These findings furnish a novel MMP-9-mediated pathway and its inhibition via proinflammatory cytokines by famotidine in ethanol-induced gastric ulceration.

Nocturnal therapy with famotidine for 1 year is effective in preventing relapse of gastric ulcer

A multicentre, double-blind, randomized, placebo-controlled trial was undertaken to investigate the therapeutic efficacy of a nocturnal dose of famotidine 20 mg to reduce the 1 year relapse rate of recently healed gastric ulcers. Twenty investigators in eight countries randomized 202 patients with endoscopically confirmed healed gastric ulcers. Repeat endoscopies were performed at 6 and 12 months or for symptoms compatible with ulcer relapse. A per protocol analysis of cumulative life table relapse at 12 months showed that famotidine 20 mg was superior to placebo in reducing gastric ulcer relapse, 24 versus 50%, respectively (P less than 0.01). Both placebo and famotidine were well tolerated. Since nocturnal dosing with famotidine 20 mg is effective in preventing gastric ulcer relapse over a 1-year period and is well tolerated, it offers a therapeutic option for the long-term treatment of patients with gastric ulcer.

Further Information on the Administration of H2-Receptor Antagonists With Atazanavir

To the Editor: Further data on the use of atazanavir (ATV) with H2-receptor antagonists and proton pump inhibitors (PPIs) have become available since the letter published by Drs. Homayoun Khanlou and Charles Farthing.1 Previously, ATV and PPI interaction studies demonstrated that ATV exposures were reduced by more than 70%, leading to a recommendation that PPIs should not be used concomitantly with ATV.2,3 Studies to evaluate other dosing strategies with ATV and PPIs are planned. More recently, data have become available on the interaction between ATV and H2-receptor antagonists, indicating that reduced exposures to ATV resulting from an interaction with H2-receptor antagonists may be attenuated by concurrent use of low-dose ritonavir (RTV) or by temporal separation from an H2-receptor antagonist.4 In 2 drug interaction studies of 108 HIV-negative subjects, the effect of the commonly used H2-receptor antagonist famotidine at 40 mg twice daily on ATV at 400 mg and ATV/RTV at 300/100 mg was evaluated.4 Relative to a control arm of ATV at 400 mg alone, coadministration of famotidine at 40 mg twice daily decreased ATV exposures by approximately 40%. Temporal separation (dosing ATV 10 hours after and 2 hours before the famotidine dose) attenuated the reduction in ATV exposures. Furthermore, ATV at 300 mg coadministered with RTV at 100 mg led to a 79% and 4.5-fold increase in area under the curve and Cmin, respectively, with Cmax values similar to ATV at 400 mg alone. Relative to a control arm of ATV/RTV at 300/100 mg alone, coadministration with famotidine at 40 mg twice daily modestly reduced ATV exposures by 18%, 14%, and 28% for area under the curve, Cmax, and Cmin, respectively. These exposures were similar to an antiretroviral regimen of ATV/RTV with 2 nucleosides including tenofovir, the efficacy of which has been established in a well-controlled study in HIV-infected subjects relative to a standard of care regimen.5 Thus, ATV/RTV at 300/100 mg may be given concomitantly in combination with H2-receptor antagonists. Atazanavir/RTV at 300/100 mg is recommended with H2-receptor antagonists, although the reductions in ATV exposures with maximal doses of famotidine could be overcome by increasing the dose of ATV to 400 mg while keeping the dose of RTV steady at 100 mg. Atazanavir/RTV at 400/100 mg is not recommended because there is a potential for increased risk of ATV intolerability, resulting from increased ATV exposures that could occur with less potent, lower doses, or sporadic dosing of H2-receptor antagonists in combination with higher doses of ATV. To further minimize any reduction in ATV exposures, an alternative to simultaneous dosing of H2-receptor antagonists with ATV/RTV at 300/100 mg is temporal separation, which may be attained by administering ATV/RTV at 300/100 mg at least 10 hours after and at least 2 hours before an H2-receptor antagonist; temporal separation should be considered in treatment-experienced patients. In summary, although H2-receptor antagonists increase intragastric pH and have been shown to reduce ATV absorption, H2-receptor antagonists are less potent than PPIs in suppressing intragastric acid secretion and may be used with ATV. Atazanavir/RTV at 300/100 mg may be administered concomitantly with H2-receptor antagonists. Alternatively, ATV at 400 mg or ATV/RTV at 300/100 mg may be temporally separated by administering ATV at least 10 hours after and at least 2 hours before an H2-receptor antagonist to minimize the interaction; temporal separation of ATV/RTV at 300/100 mg should be considered in treatment-experienced patients. Local prescribing information may vary; therefore, clinicians using ATV with H2-receptor antagonists should consult their local package inserts for specific information. Additional studies to evaluate alternative dosing strategies with ATV and H2-receptor antagonists are ongoing. Sangeeta Agarwala, PhD* Gary Thal, MD† Richard Nettles, MD* Richard Bertz, PhD* *Bristol-Myers Squibb Co, Princeton, NJ and †Bristol-Myers Squibb Co, Plainsboro, NJ [email protected]

Antiulcer effect of amlodipine and its interaction with H2blocker and proton pump inhibitor in pylorus ligated rats

<b>Objective:</b> To study the interaction between a calcium channel blocker, amlodipine, and antiulcer agents, famotidine and omeprazole, in pylorus ligation-induced gastric ulcers in rats.<br><b> Materials and Methods: </b> Gastric ulcers were induced in albino rats by pyloric ligation as described by Shay <i> et al</i> . Effects of different doses of amlodipine, famotidine and omeprazole on volume, pH, acidity of gastric secretion and ulcer index were observed. In addition, the effects of low dose of amlodipine in combination with low dose of famotidine or omeprazole on the above parameters were studied.<br><b> Results: </b> Amlodipine (0.5 mg and 1 mg/kg, i.p.), famotidine (4 mg/kg, i.p.) and omeprazole (4 mg/kg, i.p.) produced significant antiulcer effects. Low doses of famotidine (1 mg/kg, i.p.), omeprazole (1 mg/kg, i.p.) and amlodipine (0.25 mg/kg, i.p.) did not alter the above parameters significantly. Combined administration of low dose of amlodipine (0.25 mg/kg) and famotidine (1 mg/kg) showed significant antiulcer effects, which were apparent from the reduction in volume of gastric acid secretion, acidity and ulcer index with simultaneous increase in the intragastric pH. Similarly, low dose of omeprazole (1 mg/kg) when combined with low dose of amlodipine (0.25 mg/kg) also showed significant antiulcer effects.<br><b> Conclusion: </b> Amlodipine produced significant antiulcer effects in pylorus-ligated model. Combination of low doses of amlodipine with low doses of either famotidine or omeprazole produced significant antiulcer effects. It is suggested that the patients who received amlodipine therapy for some other clinical conditions are less prone to develop peptic ulcers; and even if ulcers develop, they would require lower doses of antiulcer agents like famotidine and omeprazole.

Use of Famotidine in Adult Patients with End-Stage Renal Disease: Assessment of Dosing and Mental Status Changes

Famotidine dosage adjustment is required in patients with chronic kidney disease. Since recommendations on the degree of famotidine dose reduction vary between references, a chart review was conducted to evaluate the tolerability of varying famotidine doses in adults with end-stage renal disease (ESRD). An assessment was made of famotidine doses prescribed to patients with ESRD over a 7-year period in a university hospital. Patient medical records were reviewed for evidence of mental status changes associated with famotidine. In 38 patients who met study criteria, 35 had no evidence of mental status change while receiving famotidine therapy. Among these 35 patients, the mean dose of famotidine was 24 mg/daily for 5.5 days. Three patients had mental status changes possibly associated with famotidine therapy. In this study, most ESRD patients seemed to tolerate famotidine 20 mg daily well, but larger prospective studies need to be done before final recommendations can be made. A small percentage of patients may require further dose reduction to minimize risk of mental status change.

Pharmacokinetics of Famotidine in Infants

Although famotidine pharmacokinetics are similar in adults and children older than 1 year of age, they differ in neonates owing to developmental immaturity in renal function. Little is currently known about the pharmacokinetics of famotidine in infants aged between 1 month and 1 year, a period when renal function is maturing. To characterise the pharmacokinetics of famotidine in infants. This was a two-part multicentre study with both single dose (Part I, open-label) and multiple dose (Part II, randomised) arms. Thirty-six infants (20 females and 16 males) who required treatment with famotidine and who had an indwelling arterial or venous catheter for reasons unrelated to the study. Infants in Part I were administered a single dose of famotidine 0.5 mg/kg; the dose was intravenous or oral according to the judgement of the attending physician. Infants receiving 0.5 mg/kg intravenously were divided into two groups by age, and pharmacokinetic parameters in infants 0-3 months and >3 to 12 months of age were compared. Infants in Part II were randomised to one of the following treatments: 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 and subsequent days, or 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 followed by doses of either 0.5 mg/kg/dose intravenously or 1 mg/kg/dose orally on subsequent days. From day 2 onwards, age-adjusted dose administration regimens (once daily in infants <3 months of age and every 12 hours in infants >3 months of age) were used; the total number of famotidine doses ranged from 3 to 11 and the total number of days of dose administration ranged from two to eight. In infants <3 months of age, plasma and renal clearance of famotidine were decreased compared with infants >3 months of age. Pharmacokinetic parameters for the older infants (i.e. those >3 months) were similar to those previously reported for children and adults. Approximate dose-proportionality, no accumulation on multiple dosing and an estimated bioavailability similar to adult values were also observed. A short course of famotidine therapy in infants appears generally well tolerated, and the characteristics of famotidine pharmacokinetics during the first year of life are explained to a great degree by the development of renal function, the primary route of elimination for this drug.

동아가스터 정(파모티딘 20 mg)에 대한 베스티딘 정의 생물학적동등성

A bioequivalence study of tablets (Choong Wae Pharma. Corp., Korea) to Dong-A (Dong-A Pharmaceutical Co., Ltd., Korea) tablets was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the famotidine dose of 40 mg in a crossover study. There was a one-week wash out period between the doses. Plasma concentrations of famotidine were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. (the area under the plasma concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed and . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the ratio and the Cmax ratio for were log 0.90-log 1.06 and log 0.98-log 1.20, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of and with respect to the rate and extent of absorption.

Duodenal embedment of an ingested bay leaf: an unusual cause of acute abdominal pain

The efficacy of proton pump inhibitors in patients at high risk of gastrointestinal injury receiving non-steroidal anti-inflammatory drugs is currently debated.To evaluate the effects of esomeprazole on the impairment of gastric ulcer healing associated with non-steroidal anti-inflammatory drug treatment.Gastric ulcers were induced in rats by acetic acid. Four days later, animals were treated daily with equivalent acid-inhibiting doses of esomeprazole or famotidine, alone or in combination with indomethacin. At day 3 or 7 of treatment, ulcerated tissues were processed to assess: ulcer area; malondialdehyde; prostaglandin E2; nuclear factor-kB; proliferating cell nuclear antigen and caspase-3 (Western blot).In indomethacin-treated animals, esomeprazole was more effective than famotidine or the antioxidant melatonin in promoting ulcer healing. Malondialdehyde levels were increased by indomethacin, and this effect was counteracted by esomeprazole, but not famotidine. Esomeprazole and famotidine, given alone or in combination with indomethacin, increased proliferating cell nuclear antigen expression. Increased levels of prostaglandin E2 were detected in ulcerated tissues. Ulcer prostaglandin E2 production was reduced by indomethacin, alone or in combination with esomeprazole or famotidine, while it was enhanced when esomeprazole or famotidine were tested alone. The activation of caspase-3 was induced by indomethacin, and this effect was prevented by esomeprazole, but not famotidine. In the presence of indomethacin, esomeprazole, but not famotidine, enhanced nuclear factor-kB activation in gastric ulcers.Esomeprazole counteracts the detrimental action of indomethacin on ulcer repair through both acid-dependent and acid-independent effects. The acid-independent actions are related to decrease in tissue oxidation and apoptosis and to enhancement of nuclear factor-kB activation.

Famotidine does not induce long QT syndrome: experimental evidence from in vitro and in vivo test systems

The effects of famotidine on the cardiac repolarization process were assessed using four different levels of test systems described in the draft stage guideline ICH S7B. A supratherapeutic concentration of famotidine (10 −5 M), which is >8 times higher than C max obtained after its therapeutic dose, neither inhibited human ether-a-go-go-related gene (HERG) K + current expressed in human embryonic kidney 293 (HEK293) cells nor affected any of the action potential parameters of guinea pig papillary muscles. Therapeutic (0.3 mg/kg, i.v.) to supratherapeutic doses (3–10 mg/kg, i.v.) of famotidine did not affect the repolarization process of the halothane-anesthetized canine model, while only supratherapeutic doses exerted the positive chronotropic, inotropic and dromotropic effects without affecting the mean blood pressure. Moreover, supratherapeutic doses of famotidine (1–10 mg/kg, i.v.) neither induced torsades de pointes nor prolonged QT interval in the canine chronic atrioventricular conduction block model. These results suggest that famotidine possesses no cardiovascular effects at a therapeutic dose, while it may exert cardiostimulatory actions after drug overdoses that might potentiate the proarrhythmic potential of co-administered cardiotonic agents by increasing the intracellular Ca 2+ concentration.