Selective binding of sucralfate to gastric ulcer in man

Nakazawa, Saburo; Nagashima, Ryuichi; Samloff, I. Michael

doi:10.1007/bf01308368

Cited by 96 publications

(19 citation statements)

References 3 publications

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“…The use of SOS for our studies seems reasonable in view of the observation that sucralfate, when placed in the acid milieu of the stomach, dissociates into its components aluminum ions and SOS [21]. The usual therapeutic doses of sucralfate are capable of producing local concentrations of SOS in the ranges described in our studies Figure 5, represent means f standard error from five separate perfusions.…”

Section: Commentsmentioning

confidence: 60%

Sucrose octasulfate stimulates gastric somatostatin release

Lucey

Park

DelValle

et al. 1991

The American Journal of Medicine

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To explore the mechanisms of the effects of sucralfate on the stomach, we investigated the action of sucrose octasulfate (SOS), a constituent of sucralfate, on the function of canine gastric parietal cells and somatostatin cells and in the isolated perfused intact rat stomach. Somatostatin cells from the canine gastric fundus were isolated by EDTA-collagenase dispersion and counterflow elutriation, and somatostatin-like immunoreactivity (SLI) release in response to SOS was measured by radioimmunoassay. Similar methods were used to isolate gastric parietal cells, in which gastric acid secretion was measured by uptake of a radiolabeled weak base, [14Claminopyrine.SLI release by the intact rat stomach was examined in an isolated vascularly perfused rat stomach model. SOS, either alone or co-administered with epinephrine or gastrin heptadecapeptide (Gli'), dose-dependently stimulated SLI release by isolated canine fundic D-cells. At the highest doses, SOS potentiated the effect of epinephrine but not 617. Similarly, SOS potentiated the stimulating effect of dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), but not 12-O-tetradecanoylphorbol 13-acetate (TPA). The effect of SOS on SLI release could be inhibited by octreotide, a somatostatin analogue. SOS did not alter acid secretion by cultured canine parietal cells either in the basal state or when coadministered with acid secretagogues. In isolated perfused rat stomach studies, SOS produced a significant (60% greater than basal) increase in SLI secretion. There was a similar effect when SOS was perfused against a background of isoproterenol. SOS stimulates SLI release from gastric somatostatin cells and from the isolated perfused stomach but has no direct effect on gastric

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Section: Commentsmentioning

confidence: 60%

Sucrose octasulfate stimulates gastric somatostatin release

Lucey

Park

DelValle

et al. 1991

The American Journal of Medicine

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“…Hydrochloric acid changes a coarse dispersion of sucralfate into a particulate aggregation and finally produces a sucralfate paste (31) which binds to the gastric mucosa (30,32). Tarnawski et al (45) have shown, using scanning and transmission electron microscopy, that sucralfate masses are scattered on the surface of gastric mucosa after sucralfate administration.…”

Section: Resultsmentioning

confidence: 99%

“…The healing rates following sucralfate treatment of ulceration are comparable to those associated with the use of H 2 -receptor blockers and proton pump inhibitors (PPIs), and the relapse rates are low (16,17,20,21,23,37). Sucralfate binds to the gastric mucosa, which results in the inhibition of pepsin activity (5,18,32) and the enhancement of prostaglandin synthesis (5,7,32). Furthermore, sucralfate therapy increases gastroduodenal mucus and bicarbonate secretion (6,7) and suppresses acid diffusion (3).…”

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confidence: 99%

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Effect of Sucralfate on Antibiotic Therapy for Helicobacter pylori Infection in Mice

Watanabe¹,

Murakami²,

Sato³

et al. 2004

Antimicrob Agents Chemother

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It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.Sucralfate has traditionally been classified as a topical siteprotective or cytoprotective agent of ulcer-healing drugs with a high affinity for the gastric mucosa (18,28,29,45). The healing rates following sucralfate treatment of ulceration are comparable to those associated with the use of H 2 -receptor blockers and proton pump inhibitors (PPIs), and the relapse rates are low (16,17,20,21,23,37). Sucralfate binds to the gastric mucosa, which results in the inhibition of pepsin activity (5, 18, 32) and the enhancement of prostaglandin synthesis (5, 7, 32). Furthermore, sucralfate therapy increases gastroduodenal mucus and bicarbonate secretion (6, 7) and suppresses acid diffusion (3). On contact with gastric acid, sucralfate becomes a highly condensed, viscous substance with the capacity to buffer acid and adheres to the surfaces of normal and defective mucosae (29, 45). A complex of sucralfate and extracellular mucus forms an impenetrable barrier locally (15,45). The binding of sucralfate results from the electrostatic or ionic binding of the negatively charged molecules to the positively charged proteins in the mucus or ulcer crater (30). Although mucus glycoprotein is typically negatively c...

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“…[2][3][4] Sucralfate appears to have six to seven times greater affinity for the ulcer crater than for normal mucosa. [5][6][7][8] Possible mechanisms of action of sucralfate at the ulcer site include protection of the ulcer from acid, reduction of peptic activity, and absorption of bile acids. 4,[9][10][11][12][13][14] Sucralfate is poorly absorbed from the gastrointestinal tract.…”

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confidence: 99%

Sucralfate in Duodenal Ulcer Disease: A Double-Blind Trial

1988

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Seventy-five patients with endoscopically confirmed duodenal ulcer disease received either sucralfate (34 patients) or placebo (41 patients) for 6 weeks in a double-blind clinical trial. Nineteen males and 15 females received sucralfate, and 29 males and 12 females received placebo. At 6 weeks significantly more complete ulcer healing had occurred in patients receiving sucralfate (82.4%) compared with those receiving placebo (24.4%). The sucralfate group had a significant reduction in their symptoms after 1 week of the drug intake, compared to the placebo group in which the reduction did not reach significance. Constipation, nausea, dry mouth, and skin rash occurred more in patients taking sucralfate compared to the placebo group; in one patient constipation was severe enough to stop the medicine and drop out of the trial. Systemic aluminum toxicity, hypophosphatemia, and diarrhea were not reported in any patient in the sucralfate group. MM Shennak, TM Al-Sheikh, MT Abu-Rajab, Sucralfate in Duodenal Ulcer Disease: A Double-Blind Trial. 1988; 8(6): 443-447 MeSH KEYWORDS: Sucralfate; Duodenal ulcer Sucralfate is the basic aluminum salt of sucrose substituted with eight sulfate groups.1 The sucrose part of the molecule binds to the defective mucosa and forms a protective barrier at the ulcer site.2-4 Sucralfate appears to have six to seven times greater affinity for the ulcer crater than for normal mucosa.5-8 Possible mechanisms of action of sucralfate at the ulcer site include protection of the ulcer from acid, reduction of peptic activity, and absorption of bile acids. 4,9-14 Sucralfate is poorly absorbed from the gastrointestinal tract. 9,15,16 Subjects and MethodsStudy tablets containing either sucralfate or placebo were packaged by the manufacturer in numerically labeled containers. The sucralfate tablets contained 1000 mg of the active agent. The placebo tablets contained only inert ingredients consisting of cornstarch, magnesium stearate, and microcrystalline cellulose. The identity of the study medications was unknown to the investigators, their staffs, and the patients. The patients received no other medications and were asked not to take any other antiulcer medicine.Ninety-six patients with active duodenal ulcer disease confirmed by endoscopy participated in the study. Mean age in the sucralfate patient group was 39.32 ± 12.43 years and in the placebo patients was 39.24 ± 12.91 years. The youngest patient was 18 years old, and the oldest 70 years. They were examined and evaluated within 24 hours of ulcer detection, informed of the plan and purpose of the study, and asked to participate. The evaluation consisted of a complete medical history, physical examination, and laboratory studies including complete relevant blood, stool,

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Selective binding of sucralfate to gastric ulcer in man

Cited by 96 publications

References 3 publications

Sucrose octasulfate stimulates gastric somatostatin release

Sucrose octasulfate stimulates gastric somatostatin release

Effect of Sucralfate on Antibiotic Therapy for Helicobacter pylori Infection in Mice

Sucralfate in Duodenal Ulcer Disease: A Double-Blind Trial

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