New pharmacological agents for the treatment of gastro‐oesophageal reflux disease

Vakil, Nimish

doi:10.1111/j.1365-2036.2004.01957.x

Cited by 76 publications

(38 citation statements)

References 73 publications

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“…Bilirubin and impedance monitoring are valuable in the detection of biliary reflux and non-acid reflux in such patients [40,55]. Other drugs can be used in these cases, such as the GABA(B) agonist baclofen [56][57][58]. Baclofen decreases acid and non-acid postprandial gastroesophageal reflux measured by combined multichannel intraluminal impedance and pH in both healthy volunteers and reflux patients [40].…”

Section: Non-responders To Ppi Therapymentioning

confidence: 99%

Treatment of Gastroesophageal Reflux Disease in Adults: An Individualized Approach

Galmiche

Stephenson²

2004

Dig Dis

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Until the 1990s, most therapeutic trials in gastroesophageal reflux disease (GERD) focussed upon endoscopic lesions. In fact the correlation between patient symptoms and both the presence and grade of esophagitis is very poor. The classical criteria for the assessment of therapeutic efficacy in GERD have therefore been revised, and there is now a consensus that the relief of symptoms and the long-term control of the disease are the primary aims of therapy for the majority of patients. Proton pump inhibitors (PPIs) represent the mainstay of therapy for patients with non-erosive reflux disease (NERD) as well as esophagitis. Although a stepwise strategy has been recommended in the past, a step-down strategy (starting with a full-dose PPI) appears to be a more cost-effective approach. There are as yet insufficient data to establish the clear superiority of one PPI over others. PPIs have a number of limitations. Symptom relief is significantly inferior in NERD than in erosive esophagitis. The heterogeneity of the NERD group may be one of the most influential factors, but the role of esophageal hypersensitivity has been suggested especially in patients with normal acid exposure. The role of non-acid reflux should also be scrutinized. Long-term control of the disease can be achieved by drug therapy, anti-reflux surgery and now with a variety of endoscopic procedures. The different drug management strategies can be divided into (i) continuous maintenance therapy and (ii) discontinuous therapy which can again be divided into two categories, intermittent and on-demand drug therapy. A case-by-case approach is recommended to determine the personal therapeutic needs and preferences of each individual. Many patients with NERD or mild esophagitis do not require continuous maintenance therapy and recent studies have shown excellent results with different PPI on-demand therapy regimens. Finally when making a choice between different long-term strategies both the clinician and the informed patient have to consider efficacy, safety, tolerability and cost. The potential efficacy of new drugs, especially the GABA(B) agonists and the fast onset acid suppressors, as well as the cost-effectiveness of non-drug strategies (surgery and endoluminal therapies) should be further evaluated.

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Section: Non-responders To Ppi Therapymentioning

confidence: 99%

Treatment of Gastroesophageal Reflux Disease in Adults: An Individualized Approach

Galmiche

Stephenson²

2004

Dig Dis

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“…In contrast to PPIs, a new class of acid suppressants known as potassium-competitive acid blockers (P-CABs) or acid pump antagonists inhibit gastric H ϩ , K ϩ -ATPase in a K ϩ -competitive and reversible manner (Vakil, 2004;Andersson and Carlsson, 2005;Geibel, 2005). 3-(Cyanomethyl)-2-methyl,8-(phenylmethoxy)imidazo(1,2-a)pyridine (SCH28080), a prototype P-CAB, binds to the phosphoenzyme with an extracytosolic conformation of the monovalent cation site (E 2 P) of the H ϩ , K ϩ -ATPase and is strictly K ϩ -competitive (Mendlein and Sachs, 1990).…”

Section: Introductionmentioning

confidence: 99%

A Study Comparing the Antisecretory Effect of TAK-438, a Novel Potassium-Competitive Acid Blocker, with Lansoprazole in Animals

Hori¹,

Matsukawa²,

Takeuchi³

et al. 2011

J Pharmacol Exp Ther

137

108

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Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. However, several medical needs such as suppression of night-time acid secretion and rapid symptom relief remain unmet. In this study, we investigated the effects of 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-Nmethylmethanamine monofumarate (TAK-438), a novel potassium-competitive acid blocker, on acid secretion in rats and dogs under various conditions, in comparison with the PPI, to characterize the antisecretory action of TAK-438. TAK-438 showed a more potent and longer-lasting inhibitory effect than lansoprazole on the histamine-stimulated gastric acid secretion in rats and dogs. A pharmacokinetic study in rats showed that TAK-438 accumulated and was retained in the gastric tissue for more than 24 h, unlike that in the plasma. TAK-438 showed significant antisecretory activity with or without cimetidine pretreatment, in contrast to lansoprazole, which did not show antisecretory activity after cimetidine pretreatment in rats. TAK-438 increased the pH of the gastric perfusate to 5.7 in an unstimulated condition, and this effect was maintained in the presence of subsequent histamine stimulation. On the other hand, lansoprazole also increased the pH in an unstimulated condition, but this effect diminished after histamine stimulation. These results indicated that TAK-438 exerted a more potent and longer-lasting antisecretory effect than lansoprazole through high accumulation and slow clearance from the gastric tissue. In addition, TAK-438 was unaffected by the gastric secretory state, unlike PPIs. Therefore, TAK-438 can provide a novel mechanism of action to improve the present PPI-based treatment of acid-related diseases.

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“…15 Adequate symptomatic control and patient satisfaction can be lacking in a small minority. The dissatisfaction in this group may occur due to low or non-acid reflux, or may stem from ancillary symptoms which may be functional or dysmotility-related (IBS).…”

Section: Discussionmentioning

confidence: 99%

Frequency scale symptoms for gastroesophageal reflux disease (Frequency Scale for Symptoms of GERD) predicts need for addition of prokinetics to proton pump inhibitor therapy

Nandurkar¹

2008

J of Gastro and Hepatol

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New pharmacological agents for the treatment of gastro‐oesophageal reflux disease

Cited by 76 publications

References 73 publications

Treatment of Gastroesophageal Reflux Disease in Adults: An Individualized Approach

Treatment of Gastroesophageal Reflux Disease in Adults: An Individualized Approach

A Study Comparing the Antisecretory Effect of TAK-438, a Novel Potassium-Competitive Acid Blocker, with Lansoprazole in Animals

Frequency scale symptoms for gastroesophageal reflux disease (Frequency Scale for Symptoms of GERD) predicts need for addition of prokinetics to proton pump inhibitor therapy

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