To define the basic antisecretory profile of a potassium-competitive antagonism of the gastric acid pump relative to other classes of acid-inhibitory drugs, they were compared to each other against all three major stimuli of acid secretion. Pumaprazole is an imidazo-pyridine derivative that was used in this investigation as an example of reversibly binding acid pump antagonists (APAs). It differs from covalently binding proton pump inhibitors (PPIs), such as omeprazole, both with respect to chemical structure and mode of interaction with the gastric H+/K+-ATPase (i.e., the acid or proton pump). The present data show that a single dose of pumaprazole is able to elevate intragastric pH in the dog with gastric fistula under pentagastrin or carbachol stimulation from pH 1 to about pH 7 while still displaying a dose-dependent, well-controlable duration of action of a few hours. Ranitidine at the same oral dose also shows a short duration of action, but combined with a far lower efficacy. By contrast, a single oral dose of the PPI omeprazole elevates intragastric pH for a longer time period, but this pH elevation is far lower compared to that of the APA. Regarding the less stringent parameter of inhibition of total acid output in the Heidenhain pouch dog, the modified Shay rat or the Ghosh-Schild rat, pumaprazole is, overall, slightly more efficacious than ranitidine. The M1-muscarinic antagonist pirenzepine is ineffective (against histamine stimulation) or far less effective than pumaprazole (against pentagastrin-stimulation), but as effective as pumaprazole against carbachol stimulation in the Ghosh-Schild rat. Basal acid output in the same model is more effectively inhibited by pumaprazole than by ranitidine. In conclusion, our data demonstrate the exceptional ability of a reversibly binding APA to elevate intragastric pH up to neutrality even upon a first administration while still displaying a limited, dose-dependent duration of action.

01 Jan 1999·Alimentary Pharmacology & TherapeuticsQ1 · MEDICINE

Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Helicobacter pylori infection

Q1 · MEDICINE

Article

Author: J Martínek ; M Stolte ; R Lühmann ; M Hartmann ; G Dorta ; P Wiesel ; A L Blum ; E F Verdú

Background:Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure.Aim:To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell.Methods:In a randomized, crossover, double‐blind study, 24‐h intragastric pH was measured in 13 H. pylori‐positive subjects before and after a 1‐week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured.Results:In the absence of drug administration, the median 24‐h pH values before cure (median 2.0, 90% CI: 1.2–3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3–2.2; P = 0.115). The 24‐h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8–6.7 vs. 4.3, 2.6–5.7; P = 0.002) and omeprazole (5.8, 4.0–6.2 vs. 3.6, 2.8–5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24‐h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 × 10–4– 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 × 10–3–1.5; P = 0.6).Conclusions:Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24‐h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH‐increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.

The Yale journal of biology and medicineQ4 · ENGINEERING & TECHNOLOGY

Duodenal ulcer and gastroesophageal reflux disease today: long-term therapy--a sideways glance.

Q4 · ENGINEERING & TECHNOLOGY

Review

Author: Bardhan, K D

Acid-peptic disease is widely considered conquered or controlled, future advances being refinements of existing treatments rather than radical new developments. Yet controversies remain and developments have yet to be made. DUODENAL ULCER: Daily maintenance treatment with the anti-secretory drugs, histamine H2 receptor antagonists and proton pump blockers, controls duodenal ulcer effectively, markedly reducing relapse rate at one year after treatment from about 75 percent to 15 to 20 percent (and to about 10 percent on proton pump blockers). In contrast, Helicobacter pylori eradication with a one to two week course of treatment yields prolonged remission or cure. The consequent reduction in drug costs in individual patients, however, has been exceeded by increasing community use on the more expensive proton pump blockers for the treatment of gastroesophageal reflux disease. The marked decline in elective surgery since the introduction of histamine H2 receptor antagonists is commonly attributed to the power of these drugs. The fall, however, had started much earlier, indicating that the decline is due to changing natural history. In contrast, complication rates remain unaltered. An increasing proportion of newly diagnosed duodenal ulcer patients are elderly, and more of them now present for the first time with complications (in this center, about 40 percent), which consequently cannot be forestalled. Thus, duodenal ulcer disease is likely to remain a problem and in many will be a serious illness. GASTROESOPHAGEAL REFLUX DISEASE: The proton pump blockers have revolutionized the treatment of gastroesophageal reflux disease. In clinical trials they have proven markedly superior to the histamine H2 receptor antagonists in healing (at eight weeks, 80 to 90 percent vs. 50 to 60 percent), symptom relief, prevention of relapse on maintenance therapy and cost-effectiveness. However, several issues remain. The prevalence of gastroesophageal reflux disease seems to be rising and is now probably the commonest acid-peptic disease encountered in the West. Most clinical trials comparing proton pump blockers vs. histamine H2 receptor antagonists have been done in patients with erosive esophagitis, whereas the majority (50 to 60 percent) of patients with gastroesophageal reflux disease have milder, generally non-erosive, disease. The therapeutic gain of proton pump blockers diminishes in mild disease so may not be worth the higher drug costs. This is an important area for investigation. The majority of patients with erosive esophagitis relapse when treatment is stopped (about 75 percent at one year). Relapse is markedly reduced (to 20 to 25 percent) by daily maintenance treatment with proton pump blockers. Mild disease relapses less often, so longterm therapy by intermittent treatment may prove acceptable and more cost-effective than maintenance treatment. This strategy remains unexplored in trials. The ideal profile of an anti-secretory drug for intermittent treatment would combine rapid onset of action (similar to histamine H2 receptor antagonists) with powerful effect (as with proton pump blockers). The new class of drug, the reversible proton pump blocker (e.g., BY841) approaches this requirement.

100 Deals associated with Pumaprazole

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Indication	Highest Phase	Country/Location	Organization	Date
Peptic Ulcer	Phase 3	DE	ALTANA Pharma AG	-
Stomach Ulcer	Phase 3	-	Takeda Pharmaceutical Co., Ltd.	-

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