lafutidine and Helicobacter-Infections

Lafutidine is an H2-receptor antagonist with gastroprotective action through capsaicin-sensitive afferent neurons and relatively inexpensive compare to proton-pump inhibitors (PPIs). A 7-day course of PPIs-amoxicillin-metronidazole is recommended as standard second-line Helicobacter pylori therapy and is covered by national health insurance in Japan. The aim of this study was to determine the efficacy and safety of second-line eradication using the H2-receptor antagonist lafutidine as a substitute for a PPI..  Fifty-two patients who failed in first-line eradication using PPI-amoxicillin-clarithromycin were randomly assigned to a 7-day course of rabeprazole at 10 mg b.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (RPZ-AM) or a 7-day course of lafutidine at 10 mg t.i.d., amoxicillin at 750 mg b.i.d., and metronidazole at 250 mg b.i.d. (LFT-AM) as second-line therapy. Eradication was assessed by the (13) C urea breath test. A drug susceptibility test was performed before the second-line therapy..   Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was 86.5% and the rate of resistance to metronidazole was 3.8%. The eradication rates for both LFT-AM and RPZ-AM groups were 96% (95%CI = 88.6-100%). There were no severe adverse events in either group.. Lafutidine plus metronidazole-amoxicillin as second-line therapy provided a high eradication rate and safe treatment similar to a PPI-based regimen. Lafutidine-based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Pilot Projects; Piperidines; Pyridines; Rabeprazole; Time Factors; Young Adult

Lafutidine is a novel H(2)-receptor antagonist with gastroprotective activity that includes enhancement of gastric mucosal blood flow. The aim of the present study was to test the efficacy of 7- or 14-day lafutidine-clarithromycin-amoxicillin therapy versus a lansoprazole-based regimen for Helicobacter pylori eradication.. Four hundred and sixty-three patients with H. pylori-infected peptic ulcer disease were randomized to one of four regimens: (1) lafutidine (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LFT group) or (2) for 14 days (the 14LFT group); (3) lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LPZ group); or (4) for 14 days (the 14LPZ group). The eradication rates, drug compliance, and adverse effects among the four regimens were compared.. The eradication rates by the intention-to-treat and per-protocol analyses in the 7LFT and 7LPZ groups were 76.5% and 81.6%, and 76.9% and 82.0% (p = .94 and .95), respectively. The eradication rates by intention-to-treat and per-protocol analyses in the 14LFT and 14LPZ groups were 78.2% and 82.2%, and 80.4% and 85.9% (p = .70 and .49), respectively. The treatment duration for 7 days or 14 days did not affect the eradication rates. In addition, the adverse effect rates and discontinuation rates were similar among the four groups. Furthermore, the ulcer cure rate and symptom response rate were similar in the lafutidine and lansoprazole groups.. The results of this study showed that lafutidine-clarithromycin-amoxicillin therapy was a safe and effective as lansoprazole-based triple therapy for the eradication rate of H. pylori, and could be considered as an additional treatment option.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Female; Helicobacter Infections; Helicobacter pylori; Humans; Korea; Lansoprazole; Male; Middle Aged; Piperidines; Pyridines; Time Factors; Treatment Outcome

Even with the most effective treatment, Helicobacter pylori eradication is difficult in some patients. Therefore, patients sometimes require acid-suppressive therapy without H. pylori eradication. It has been reported that ranitidine inhibits neutrophil activation, whereas famotidine does not. However, few studies have been published concerning the activation of neutrophils before and after treatment using clinical doses of histamine-2 receptor antagonists in patients with H. pylori infection.. To examine the effects of neutrophil activation after treatment with three different histamine-2 receptor antagonists.. This prospective, open-label, randomised, parallel-group study was conducted. Thirty patients with H. pylori infection were enrolled. These subjects were randomly assigned to receive one of the following treatments: (a) 150 mg ranitidine, (b) 20mg famotidine, or (c) 10 mg lafutidine b.d., for 4 weeks. Before and after histamine-2 receptor antagonist treatment, histological findings, myeloperoxidase activity, and interleukin-8 in the gastric mucosa were evaluated.. On the basis of the histological findings between before and after histamine-2 receptor antagonist treatment, no significant differences were found in any groups. Similarly, there were no significant differences in myeloperoxidase activity or interleukin-8 levels.. In patients with H. pylori, when used at clinical doses, any histamine-2 receptor antagonists can be used without concerning about inhibition of neutrophil activation.

Topics: Acetamides; Adult; Dyspepsia; Famotidine; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Peroxidase; Piperidines; Pyridines; Ranitidine

To investigate the therapeutic effects of triple therapy combining lafutidine with clarithromycin and amoxicillin on H pylori infection and the resolution of gastroesophageal symptoms after eradication.. We conducted a randomized, multicenter, open-label controlled trial to compare the effectiveness of a triple therapy of lafutidine, clarithromycin, and amoxicillin (lafutidine group) with that of a triple therapy of lansoprazole, clarithromycin, and amoxicillin (lansoprazole group) in patients with H pylori infection. The study group comprised 22 patients with gastric ulcers and 18 patients with duodenal ulcers who had H pylori infection.. H pylori eradication rates were similar in the lafutidine group (14/20, 70%) and the lansoprazole group (14/20, 70%). Gastroesophageal reflux and abdominal symptoms improved after eradication therapy in both groups, whereas abdominal discomfort, diarrhea, and constipation were unchanged. H pylori status had no apparent effect on improvement of gastroesophageal reflux or abdominal symptoms after treatment. Adverse events were similar in both groups.. The triple therapy including lafutidine is equivalent to triple therapy including lansoprazole in terms of H pylori eradication rates and improvement in gastroesophageal reflux and abdominal symptoms. These results are attributed to the fact that lafutidine has strong, continuous antisecretory activity, unaffected by CYP2C19 polymorphisms.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Infective Agents; Clarithromycin; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Male; Middle Aged; Piperidines; Pyridines

The attenuated anti-secretory activity of H2 receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. However, it is not clarified whether Helicobacter pylori infection affects the occurrence of tolerance to H2RA. It is also not clarified whether the tolerance phenomenon occurs to a new H2RA, lafutidine.. To investigate the occurrence of the tolerance phenomenon in subjects with and without H. pylori infection during the continuous administration of lafutidine and famotidine.. Subjects were 20 healthy male volunteers (seven H. pylori positive and 13 H. pylori negative cases). All subjects were examined by ambulatory intragastric pH monitoring five times without medication, on the first and 15th day of the administration of 20 mg b.d. famotidine and 10 mg b.d. lafutidine in a cross-over fashion.. The tolerance phenomenon was not observed in H. pylori-positive subjects during the 15-day-long administration of both H2RAs. In contrast, the tolerance phenomenon was observed in H. pylori negative subjects, which has been previously reported.. This study demonstrated that H. pylori infection affects the tolerance phenomenon during continuous administration of H2RAs.

Topics: Acetamides; Adult; Ambulatory Care; Circadian Rhythm; Cross-Over Studies; Cross-Sectional Studies; Drug Tolerance; Famotidine; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Piperidines; Pyridines

In contrast to the growing amount of data concerning proton pump inhibitor-based triple therapy for Helicobacter pylori infection, it is still controversial whether proton pump inhibitor can be replaced by H2 receptor antagonist without compromising efficacy. Lafutidine is a novel potent H2 receptor antagonist with gastroprotective activities such as enhancement of gastric mucosal blood flow.. 122 outpatients with positive cultures and subsequent successful cultivation of H. pylori for antimicrobial susceptibility tests were randomized to receive a 7-day course of either lafutidine (20 mg twice daily) or lansoprazole (30 mg twice daily), plus clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Eradication was considered successful if the rapid urease test, culture, histology and [13]C-urea breath test were all negative at least 4 weeks after cessation of therapy. Cytochrome p450 2C19 genotype status using polymerase chain reaction-restriction fragment length polymorphism was also studied.. On intention-to-treat basis, H. pylori cure was achieved in 52 of 61 (85.2%) patients and 49 of 61 (80.3%) patients for the lafutidine- and lansoprazole-based therapies, respectively. The predicted 95% confidential intervals for the 4.9% of the difference were -1.8-11.6%. Using per protocol analysis, the eradication rates were 88.2% (52/59) and 84.5% (49/58), respectively. The predicted 95% confidential intervals for the 3.7% of the difference were -2.6-10.0%. Adverse events were observed in five and six patients, from the lafutidine and lansoprazole groups, respectively, but they were generally mild. Genetic predisposition of cytochrome p450 2C19 had no significant influence on treatment outcome in both regimens.. The lafutidine-clarithromycin-amoxicillin therapy yielded satisfactory results for eradicating H. pylori, which was comparable with those of the lansoprazole-based regimen with the same drug combination.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Aryl Hydrocarbon Hydroxylases; Clarithromycin; Cytochrome P-450 CYP2C19; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Lansoprazole; Male; Middle Aged; Mixed Function Oxygenases; Omeprazole; Penicillins; Piperidines; Prospective Studies; Pyridines

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetamides; Benzimidazoles; Gastric Acid; Gastric Acidity Determination; Heartburn; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Hydrogen-Ion Concentration; Omeprazole; Piperidines; Prognosis; Proton Pump Inhibitors; Pyridines; Rabeprazole; Severity of Illness Index; Treatment Outcome