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Int J Antimicrob Agents. 2002 Mar;19(3):195-200.
Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro.

Chen M, Jensen B, Zhai L, Colding H, Kharazmi A, Kristiansen JE, Andersen LP.

Department of Clinical Microbiology, Helicobacter Laboratory, Building 9301, National University Hospital (Rigshospitalet), Tagensvej 20, DK-2200 Copenhagen, Denmark.

Treatment failures are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa when triple therapy including metronidazole is used. In patients with treatment failure and metronidazole-resistant H. pylori, a higher eradication rate for H. pylori was found after secondary treatment with bismuth/ranitidine in combination with antibiotics including metronidazole, compared with the same antibiotics combined with a standard dose of omeprazole. This agrees with our previous finding that bismuth was able to reduce the susceptibility of H. pylori to metronidazole. In this study, we have found that nizatidine, an H(2)-receptor antagonist, is also able to reduce the susceptibility of H. pylori to metronidazole in vitro, despite having no direct inhibitory effect on the growth of H. pylori. This agrees with earlier findings that compounds having the ability to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit the activity of fumarate reductase of H. pylori. This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could be an inhibition of a proton pump in H. pylori. Reversal of antimicrobial resistance with the help of different non-antibiotics seems to be possible by using quite different compounds, and is therefore to be explained by different molecular mechanisms.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11932141&dopt=Abstract

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OBJECTIVES: To evaluate the cost effectiveness of on-demand treatment with esomeprazole 20mg compared with two alternative omeprazole treatment strategies for the long-term management of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis. DESIGN: A simple Markov model was designed to compare the cost effectiveness of on-demand esomeprazole 20mg therapy for 6 months with a strategy consisting of intermittent 4-week acute treatment courses of omeprazole 20mg once daily or a strategy consisting of continuous omeprazole treatment (20mg once daily) following acute treatment of first relapse while on no drug treatment (a commonly used conventional care strategy). Relapse probabilities were based on pooled results from two 6-month placebo-controlled clinical studies of on-demand esomeprazole 20mg treatment in patients with GORD without oesophagitis and on results from a GORD study with a 6-month untreated follow-up. The expected number of relapses per patient was used as the effectiveness measure. SETTING AND PERSPECTIVE: Patient management assumptions were based on a UK physician survey. The cost-effectiveness analysis considered UK direct medical costs from the perspective of the National Health Service. RESULTS: The pooled analysis showed that after 6 months treatment, 90% of patients could control symptoms effectively with on-demand esomeprazole 20mg. The expected number of relapses per patient was estimated at 0.10 for on-demand esomeprazole, 0.57 to 1.12 for intermittent omeprazole and 0.47 to 0.75 for conventional omeprazole treatment. The esomeprazole strategy incurred considerably lower direct medical costs (16 to 61%) than either omeprazole strategy. CONCLUSION: On-demand treatment with esomeprazole 20mg is cost effective compared with two alternative omeprazole treatment strategies in patients with GORD without oesophagitis.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11950383&dopt=Abstract

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astrazeneca.com

BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. METHODS: Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service. RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11950384&dopt=Abstract

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