A Phase 1, Randomized, Open-Label, Crossover Study to Evaluate the Bioequivalence of Single Oral Dose of TAK-438ASA Tablet and Single Oral Dose of TAK-438 Tablet Plus Aspirin Enteric-Coated Tablet (Study 1) and the Food Effect of Single Oral Dose of TAK-438ASA Tablet (Study 2) in Healthy Adult Male Subjects

The purposes of this study are to evaluate BE between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 milligram (mg) and aspirin enteric-coated tablet 100 mg in Japanese healthy adult men (Study 1), and to evaluate the effects of food on the pharmacokinetics of TAK-438ASA tablet in Japanese healthy adult men (Study 2).

开始日期2018-03-08

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与 H+/K+ ATPase x Proton pump x COX 相关的临床结果

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100 项与 H+/K+ ATPase x Proton pump x COX 相关的转化医学

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0 项与 H+/K+ ATPase x Proton pump x COX 相关的专利（医药）

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项与 H+/K+ ATPase x Proton pump x COX 相关的文献（医药）

2021-01-01·The Laryngoscope1区 · 医学

H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients

1区 · 医学

Article

作者: Wells, Clive ; Battle, Michele A. ; Yan, Ke ; Johnston, Nikki ; McCormick, Caroline A. ; Samuels, Tina L. ; Bock, Jonathan M. ; Frolkis, Talia ; Blumin, Joel H. ; Altman, Kenneth W.

ObjectivesThe gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects.Study DesignIn‐vitro translational.MethodsLaryngeal biopsies were obtained from three LPR and eight LSCC patients. ATP4A, ATP4B and HRPT1 were assayed via qPCR. Human hypopharyngeal FaDu cell lines stably expressing proton pump were created using lentiviral transduction and examined via transmission electron microscopy and qPCR for genes associated with inflammation or laryngeal cancer.ResultsExpression of ATP4A and ATP4B was detected in 3/3 LPR, 4/8 LSCC‐tumor and 3/8 LSCC‐adjacent specimens. Expression of ATP4A and ATP4B in FaDu elicited mitochondrial damage and expression of IL1B, PTGS2, and TNFA (P < .0001); expression of ATP4B alone did not.ConclusionsGastric proton pump subunits are expressed in the larynx of LPR and LSCC patients. Mitochondrial damage and changes in gene expression observed in cells expressing the full proton pump, absent in those expressing a single subunit, suggest that acid secretion by functional proton pumps expressed in upper airway mucosa may elicit local cell and molecular changes associated with inflammation and cancer.Level of EvidenceNA Laryngoscope, 131:130–135, 2021

2020-10-01·Life Sciences3区 · 医学

Attenuation of ischemia-reperfusion-induced gastric ulcer by low-dose vanadium in male Wistar rats

3区 · 医学

Article

作者: Tosan Peter Omayone ; Samuel Babafemi Olaleye ; James Olukayode Olopade ; Adeola Temitope Salami

AIMVanadium, a trace element found in food and water sources has been previous reported to attenuate ulcer formation without much insight into its mechanism of action. This study highlights the mechanism by which vanadium exhibits its gastro-protective activity.MAIN METHODSEighty male Wistar rats (80-100 g) were randomized into 8 equal groups. Groups 1 (control) and 2 (Ulcerated control) received water only, groups 3-8 received vanadium at 5, 10, 25, 50, 100 and 200 ppm respectively in their drinking water for ten weeks. Gastric ulcer was thereafter induced in groups (2-8) via ischaemia-reperfusion (IR) technique. The stomachs were excised for macroscopic examination, evaluation of mucous content, oxidative stress markers, hydrogen/potassium (H⁺/K⁺) and calcium (Ca⁺⁺) ATPases activities plus expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Vanadium at low doses inhibited IR induced gastric ulcer by 62.62% (10 ppm), 54.80% (25 ppm) and 43.50% (50 ppm).KEY FINDINGSLow dose vanadium increased mucous content, superoxide dismutase, catalase, glutathione activities and nitrite concentrations compared to ulcerated control group. The observed increase in malondialdehyde, Ca⁺⁺ and H⁺/K⁺ ATPase activities, iNOS and COX-2 expression following IR were significantly reduced by pretreatment with vanadium.SIGNIFICANCEThis study demonstrated that vanadium at low doses exhibit gastro-protective activities on IR induced gastric ulcer in rat model by inhibiting proton pump activities and decreasing expressions of iNOS and COX-2, thereby giving more insight into the protective action of vanadium.

2009-02-01·Clinical and Experimental Pharmacology and Physiology4区 · 医学

CYCLO‐OXYGENASE‐1 INHIBITION INCREASES ACID SECRETION BY MODULATING H⁺,K⁺‐ATPase EXPRESSION AND ACTIVATION IN RABBIT PARIETAL CELLS

4区 · 医学

Article

作者: Jyotirmoy Nandi ; Pratap K Das ; Juan D Baltodano ; J Michael Zinkievich ; Robert A Levine

SUMMARY

In the present study, we evaluated the role of cyclo‐oxygenase (COX)‐1 and COX‐2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [14C]‐aminopyrine uptake, prostaglandin (PG) E2 synthesis and COX‐1, COX‐2 and proton pump expression at baseline and after treatment with various concentrations of specific COX‐1 (SC‐560), COX‐2 (5,5‐dimethyl‐3‐(3‐fluorophenyl)‐4‐(4‐methyl‐sulphonyl)phenyl‐2 (5H)‐furanone; DFU) and non‐specific COX (indomethacin) inhibitors.

In parietal cells, SC‐560 and indomethacin, over the concentration range 10−8 to 10−4 mol/L, dose‐dependently increased basal and 10−4 mol/L histamine‐stimulated aminopyrine uptake and inhibited PGE2 synthesis, whereas DFU (10−8 to 10−5 mol/L) had no effect. However, at 10−4 mol/L, DFU augmented histamine‐stimulated aminopyrine uptake by 135% and inhibited PGE2 synthesis by 39%, indicating an inhibition of COX‐1 at this higher concentration.

The SC‐560‐, DFU‐ and indomethacin‐induced augmentation of histamine‐stimulated aminopyrine uptake was reduced to basal levels after 10−5 mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10−4 mol/L ranitidine only partially inhibited such augmentation.

Only COX‐1 was detected in parietal cells. However, both COX‐1 and COX‐2 were expressed in gastric glands, with relative protein density of COX‐1 being sixfold higher than that of COX‐2. Protein levels of COX‐1 in parietal cells and those of COX‐1 and COX‐2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine.

Parietal cell proton pump expression was significantly enhanced by 10−5 mol/L SC‐560 and 10−4 mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10−5 mol/L DFU had no effect.

In conclusion, the data indicate that inhibition of COX‐1‐ but not COX‐2‐derived PGE2 synthesis is involved in augmentation of non‐steroidal anti‐inflammatory drug‐induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump.