Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates.

Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H-receptor antagonists (HRAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs).

Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial.

Background & Aims: Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in United States subjects diagnosed with non-erosive reflux disease of vonoprazan vs placebo for 4 weeks, followed by a 20-week active-treatment extension.

Methods: Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg.

Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease.

Background: Non-erosive reflux disease (NERD) symptoms are often episodic, making on-demand treatment an attractive treatment approach.

Aims: We compared the efficacy and safety of on-demand vonoprazan versus placebo in patients with NERD.

Methods: Patients with NERD, defined as heartburn for ≥6 months and for ≥4/7 consecutive days with normal endoscopy, received once-daily vonoprazan 20 mg during a 4-week run-in period.

Brief communication: global temporal trends in the efficacy of clarithromycin-based regimens for the treatment of infection.

Background: eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce.

Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time.

Design: A comprehensive literature review and time-trend analysis.

A translational pharmacokinetic/pharmacodynamic approach supports optimal vonoprazan dosing for erosive oesophagitis and Helicobacter pylori infection.

Background: Treatment of acid-related disorders relies on gastric acid suppression. The percentage of time intragastric pH is >4 (pH >4 holding time ratio [HTR]) is important for healing erosive oesophagitis; and the pH >6 HTR is critical for eradication of Helicobacter pylori infection, as bacterial replication is active and antibiotic effectiveness is optimised. Vonoprazan, a potassium-competitive acid blocker approved in the USA and other countries, suppresses gastric acid secretion in a predictable, rapid and consistent manner, extended over prolonged periods.

Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.

Vonoprazan is metabolized extensively through CYP3A and is an in vitro time-dependent inhibitor of CYP3A. A tiered approach was applied to understand the CYP3A victim and perpetrator drug-drug interaction (DDI) potential for vonoprazan. Mechanistic static modeling suggested vonoprazan is a potential clinically relevant CYP3A inhibitor.

Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe.

Introduction: Guidelines recommend that proton pump inhibitor-based triple regimens with clarithromycin not be used for Helicobacter pylori infection in areas where clarithromycin resistance is ≥15%, or in patients with prior macrolide use. Up-to-date information on local resistance patterns is limited, especially in the US. Here, we report resistance rates to antibiotics commonly used to treat H.

Potassium-Competitive Acid Blocker and Proton Pump Inhibitor-Based Regimens for First-Line Eradication: A Network Meta-Analysis.

Background And Aims: Effective acid suppression is a crucial component of () eradication regimens. Approved treatments include dual, triple, and quadruple therapies composed of certain antibiotics in combination with proton pump inhibitors (PPIs). Vonoprazan, a potassium-competitive acid blocker, provides more potent and durable acid suppression than PPIs.

Pharmacodynamics and Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan and the Proton Pump Inhibitor Lansoprazole in US Subjects.

Introduction: We assessed pharmacodynamics and pharmacokinetics of a potassium-competitive acid blocker and proton pump inhibitor in US subjects.

Methods: Healthy adults were randomized to 7-day periods of vonoprazan 20 mg once daily followed by lansoprazole 30 mg once daily or the reverse order, separated by ≥ 7 days of washout.

Results: Vonoprazan (N = 40) had higher proportions of 24-hour periods with intragastric pH > 4 than lansoprazole (N = 41,38) on day 1 (62.

A Population Pharmacokinetic Model of Vonoprazan: Evaluating the Effects of Race, Disease Status, and Other Covariates on Exposure.

Vonoprazan, a potassium-competitive acid blocker, is under investigation in the United States and Europe for the treatment of erosive esophagitis and Helicobacter pylori infection. Population pharmacokinetic (popPK) analysis allows the identification of factors that could affect drug exposure in population subgroups. Here, we report a popPK model based on pooled data sets of available pharmacokinetic (PK) studies in healthy volunteers and patients with gastroesophageal reflux disease, including erosive esophagitis, from Asia and Europe.

The Effect of Food on the Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan.

Herein, we report a food-effect study of vonoprazan, an oral potassium-competitive acid blocker. In a phase 1, randomized, open-label, crossover study, healthy subjects received a single 20-mg dose of vonoprazan either following an overnight fast or 30 minutes after a high-fat breakfast. Plasma vonoprazan levels were determined at 0 hour and at 17 subsequent assessment points up to 48 hours after dosing.

TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial.

Background: Activation of free fatty acid receptor 1 (FFAR1; also known as G-protein-coupled receptor 40) by fatty acids stimulated glucose-dependent β-cell insulin secretion in preclinical models. We aimed to assess whether selective pharmacological activation of this receptor by TAK-875 in patients with type 2 diabetes mellitus improved glycaemic control without hypoglycaemia risk.

Methods: We undertook a phase 2, randomised, double-blind, and placebo-controlled and active-comparator-controlled trial in outpatients with type 2 diabetes who had not responded to diet or metformin treatment.

Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of the GPR40 agonist TAK-875: results from a double-blind, placebo-controlled single oral dose rising study in healthy volunteers.

TAK-875 is a selective G-protein-coupled receptor 40 agonist in development for the treatment of type 2 diabetes mellitus. This randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-875 following administration of a single oral dose of TAK-875 (25-800 mg) in 60 healthy volunteers. TAK-875 was eliminated slowly with a mean terminal elimination t(1/2) of approximately 28.

Differences in symptom scores and health outcomes in premenstrual syndrome.

Background: In studies of premenstrual syndrome (PMS), a significant response to treatment is commonly defined as a 50% reduction in symptom scores, but empirical support for this definition is lacking. We compared healthcare utilization in women with and without PMS according to the Daily Record of Severity of Problems (DRSP) scores in order to determine the degree of symptomatic variation in premenstrual symptoms associated with differences in the burden of illness.

Methods: Participants were women aged 18-45 years enrolled in a medical group in southern California.

The sensitivity of murine spermiogenesis to miglustat is a quantitative trait: a pharmacogenetic study.

Background: A major event in the post-meiotic development of male germ cells is the formation of the acrosome. This process can be perturbed in C57BL/6 mice by administration of the small molecule miglustat (N-butyldeoxynojirimycin, NB-DNJ). The miglustat-treated mice produce morphologically abnormal spermatozoa that lack acrosomes and are poorly motile.

Sex hormones in psychotic men.

For women at risk to develop schizophrenia, estradiol has been postulated to constitute a protective factor. Women suffering from psychotic disorders have accordingly been found to exhibit lower estradiol levels than controls. Our aim was to study gonadal function in psychotic men to determine the gender specificity of these observations, as available data in men are more scarce and conflicting and largely disregarded estradiol.