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Erosiv esofagit (EE) innebär uppkomst av inflammation och slemhinneskador i matstrupen. Den huvudsakliga orsaken till EE är gastroesofageal reflux (GERD), då det sura maginnehållet stöts upp i matstrupen. Bristande funktion av nedre esofagussfinktern (LES) och diafragmabråck kan också orsaka EE. Obehandlad EE kan leda till komplikationer såsom Barretts esofagus (BE), adenocarcinom, förträngning av matstrupen och gastrointestinala blödningar. Diagnostiken sker med hjälp av endoskopi. Behandlingen av EE går bland annat ut på att påskynda läkning av slemhinneskador i matstrupen. Den består huvudsakligen av läkemedelsterapi och livsstil- och kostförändringar, men även kirurgi kan vara en möjlig behandling. Läkemedelsterapi består av syrahämmande läkemedel som hämmar produktionen av magsyra. Protonpumpshämmare (PPI), till exempel lansoprazol (LPZ), är standardbehandlingen vid syrarelaterade sjukdomar, bland annat EE. PPI har dock begränsningar och upp till 20 % med svårare EE uppnår inte läkning. Vonoprazan (VPZ) tillhör kalium kompetitivasyrablockerare (P-CAB) och är ett nytt syrahämmande läkemedel som är godkänt i bland annat Japan och USA för behandling av EE. Syftet med detta litteraturarbete var att undersöka effekten av 20 mg VPZ jämfört med 30 mg LPZ efter åtta veckors behandling av EE, genom att ta del av publicerade kliniska studier. Fyra olika RCT-studier hämtade från databasen PubMed användes i detta litteraturarbete. Alla fyra studier resulterade i att VPZ inte var sämre än LPZ vid behandling av EE i upp till åtta veckor. Fler patienter i VPZ-gruppen uppnådde läkning av EE i samtliga studier. Dessutom visade VPZ ha bättre effekt hos patienter med svårare EE. Number Needed to Treat (NNT) för de olika studierna varierade mycket, därför kunde inte den användas för att beskriva den kliniska effekten av VPZ vid behandling av EE. Både VPZ och LPZ tolererades väl. Slutsatsen var att VPZ 20 mg en gång dagligen var inte sämre än LPZ 30 mg en gång dagligen vid behandli

Erosiv esofagit (EE) innebär uppkomst av inflammation och slemhinneskador i matstrupen. Den huvudsakliga orsaken till EE är gastroesofageal reflux (GERD), då det sura maginnehållet stöts upp i matstrupen. Bristande funktion av nedre esofagussfinktern (LES) och diafragmabråck kan också orsaka EE. Obehandlad EE kan leda till komplikationer såsom Barretts esofagus (BE), adenocarcinom, förträngning av matstrupen och gastrointestinala blödningar. Diagnostiken sker med hjälp av endoskopi. Behandlingen av EE går bland annat ut på att påskynda läkning av slemhinneskador i matstrupen. Den består huvudsakligen av läkemedelsterapi och livsstil- och kostförändringar, men även kirurgi kan vara en möjlig behandling. Läkemedelsterapi består av syrahämmande läkemedel som hämmar produktionen av magsyra. Protonpumpshämmare (PPI), till exempel lansoprazol (LPZ), är standardbehandlingen vid syrarelaterade sjukdomar, bland annat EE. PPI har dock begränsningar och upp till 20 % med svårare EE uppnår inte läkning. Vonoprazan (VPZ) tillhör kalium kompetitivasyrablockerare (P-CAB) och är ett nytt syrahämmande läkemedel som är godkänt i bland annat Japan och USA för behandling av EE. Syftet med detta litteraturarbete var att undersöka effekten av 20 mg VPZ jämfört med 30 mg LPZ efter åtta veckors behandling av EE, genom att ta del av publicerade kliniska studier. Fyra olika RCT-studier hämtade från databasen PubMed användes i detta litteraturarbete. Alla fyra studier resulterade i att VPZ inte var sämre än LPZ vid behandling av EE i upp till åtta veckor. Fler patienter i VPZ-gruppen uppnådde läkning av EE i samtliga studier. Dessutom visade VPZ ha bättre effekt hos patienter med svårare EE. Number Needed to Treat (NNT) för de olika studierna varierade mycket, därför kunde inte den användas för att beskriva den kliniska effekten av VPZ vid behandling av EE. Både VPZ och LPZ tolererades väl. Slutsatsen var att VPZ 20 mg en gång dagligen var inte sämre än LPZ 30 mg en gång dagligen vid behandli

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Backgrounds: Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels.Methods: Eleven healthy volunteers were subjected to 24-hour intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75mg alone, vonoprazan 10mg alone, and vonoprazan 10mg plus pirenzepine 75mg administered in a randomized crossover fashion.Results: Median pH 4 holding time ratios (range) achieved with pirenzepine 75mg, vonoprazan 10mg and vonoprazan 10mg plus pirenzepine 75mg were 6.9% (2.4–32.8%), 88.4% (54.6–100%), and 84.2% (40.3–100%), respectively. Respective serum gastrin levels were 79 (75–210) pg/ml, 310 (110–870) pg/ml, and 170 (140–930) pg/ml. In cases with hypergastrinemia (gastrin≥200pg/ml) induced by vonoprazan 10mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370pg/ml to 180pg/ml (P=0.028).Conclusion: Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.

Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer.

Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer.

Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer.

We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p=0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p=0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p=0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p=1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2019 to April 2020. The main themes that emerge involve studies assessing antibiotic resistance and there is also growing momentum behind the utility of vonoprazan as an alternative to proton pump inhibitor (PPI) therapy and also bismuth‐based regimens as a first‐line regimen.Antibiotic resistance is rising wherever it is being assessed and clarithromycin resistance in particular has reached a point where it may no longer be a viable therapy without previous testing in many regions of the world. The evidence for the efficacy of a bismuth‐based quadruple therapy as a firstline therapy is now very clearly established, and there is substantial evidence that it is the best performing first‐line therapy. The utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult‐to‐treat groups, has also been considered in great detail this year, and it may offer an opportunity in the near future to reduce the problem of antibiotic resistance.

Gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) can significantly reduce a patient's quality of life. GERD in SSc is occasionally resistant to conventional anti-acid treatment. Vonoprazan is an H+/K+-ATPase blocker that is approved in Japan for treatment of GERD. The aim of the present study was to evaluate the efficacy of vonoprazan in SSc-related GERD. The frequency scale for symptoms of GERD (FSSG) scores were collected before and after vono-prazan treatment in 15 SSc patients with GERD. Additionally, endoscopic esophagogastroduodenoscopy was performed in select patients. Conventional proton pump inhibitors or hista-mine-2 receptor antagonists had been previously administered in 93% (14/15) of the patients. Although the baseline esophago-gastroduodenoscopy examination did not show severe erosion in the majority of patients,the mean total FSSG score before vonoprazan treatment was notably high (25.2±10.7) compared to a normal score of <8. After vonoprazan treatment, the FSSG score decreased to 9.6±7.0. The mean improvement rate of the total FSSG, acid reflux and dysmotility scores were 60.8±21.2% (P=0.0004), 67.3±24.8% (P<0.0001) and 55.4±26.0% (P=0.0022), respectively.These results suggest that vonoprazan may be a potentially effective treatment for GERD in patients with SSc., Biomedical Reports, 14(2), pp.1-8; 2020