Purpose: Proton pump inhibitors (PPIs) are used for the treatment of acid-related disorders. Demands for enhanced stability and faster onset led to the development of AD-206, a fixeddose combination of a PPI (esomeprazole) with an antacid salt (calcium carbonate). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of AD-206 (Addpharma) with conventional esomeprazole (Nexium ® , AstraZeneca). Materials and Methods:A randomized, open-label, two-treatment, two-sequence crossover study was conducted with 2 different doses of esomeprazole at 20 and 40 mg with a fixed calcium carbonate dose of 600 mg in AD-206. Forty-four subjects were included in each dose group and randomly received either AD-206 or the conventional esomeprazole for 7 consecutive days in each period. After a single-and multiple-dose, blood samples for the PK analysis were analyzed, and 24-hour intragastric pH monitoring was conducted. Results:The systemic exposure of esomeprazole after a multiple-dose of AD-206 was similar to that of the conventional esomeprazole in both doses, but the time to reach the peak concentration was faster in AD-206. The percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the dose was not significantly different between the AD-206 and the conventional esomeprazole after a single-and multiple-dose for both doses, and the time to reach pH 4 was faster for AD-206. Conclusion: AD-206 showed a similar systemic exposure and suppression of gastric acid secretion after a multiple-dose compared to the conventional esomeprazole.

P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) are clinically important efflux transporters of the ATP-binding cassette (ABC) family of transporters, widely recognized for their broad substrate specificity associated with multidrug resistance in cancers and limiting substrate drug intracellular accumulation. While their expression and function in organs such as the intestine, liver and kidneys are well understood, there is little known concerning pancreatic islet cells. This study was aimed to characterize the expression and localization of P-gp and BCRP transporters in adult human pancreatic islets using quantitative reverse transcription PCR (qPCR) and dual immunofluorescent staining approaches. We showed that P-gp and BCRP were highly expressed in the islets compared to liver, and frequently colocalized with insulin or glucagon. These findings provide new insights regarding P-gp and BCRP abundance in beta and alpha cells suggesting a potential role for these efflux transporters in limiting islet cell injury to xenobiotics.

Purpose Proton pump inhibitors (PPIs) are the first-line therapy for gastroesophageal reflux disorder (GERD). Unlike conventional PPIs, non-enteric coated PPIs with antacid salt enable a faster acid suppression through the rapid absorption of the PPI. YPI-011 is a newly developed fixed-dose combination of a rabeprazole with sodium bicarbonate (NaHCO 3 ). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of YPI-011 to the conventional enteric-coated rabeprazole (Pariet ® ). Materials and Methods A randomized, open-label, two-treatment, two-sequence crossover study was conducted with two different doses (10 and 20 mg) and 44 subjects in each group. They randomly received either a test or reference treatment for 7 days in the first period and the other treatment in the second period. Blood samples for the PK analysis were taken after the single- and multiple-dose. Intragastric pH monitoring for the PD analysis was implemented for baseline and after the single- and multiple-dose. Results Gastric acid suppression evaluated by the percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the multiple-dose was similar between the treatments in both dose groups. The systemic exposure of rabeprazole at steady state after the multiple-dose was also similar between the treatments in both dose groups. The time to reach the maximum rabeprazole concentration was faster in the test treatment. The PK-PD relationship of PPI is well known, and the faster absorption of rabeprazole resulted in a more rapid mode of action in acid suppression. Conclusion The fixed dose combination of rabeprazole with NaHCO 3 showed a faster absorption and consequently, a more rapid gastric acid suppression with a similar systemic exposure of rabeprazole at steady state compared to the conventional enteric-coated rabeprazole.

AimsThe new modified‐release formulation of tegoprazan, a novel potassium‐competitive acid blocker, is expected to improve the management of acid‐related disease, including nocturnal acid breakthrough, by prolonging the duration of acid suppression. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of various combinations of tegoprazan with immediate‐release (IR) and delayed‐release (DR) formulations.MethodsA three‐cohort, open‐label, randomized, single‐dose, three‐treatment, six‐sequence, three‐period crossover study was conducted. Various combinations of tegoprazan IR and DR formulations (50, 75 or 100 mg) were administered orally once per period. The 24‐h intragastric pH was monitored before and after each administration. PK blood samples were collected for up to 48 h. PK and PD were compared among treatments.ResultsEighteen healthy Korean subjects completed the study. All treatment groups showed intragastric pH above 4 approximately 1 h following tegoprazan administration. Among the various combinations, the IR and DR combination at a 1:1 ratio induced greater gastric acid suppression (%Time pH ≥ 4) than IR alone in each dose group, both for 24 h (50 mg; 59% vs. 52%, P = .2188, 95% confidence interval [CI] −6.92–22.27, 100 mg; 85% vs. 70%, P < .05, 95% CI 8.92–22.19) and at night (50 mg; 27% vs. 16%, P = .1563, 95% CI −11.79–37.71, 100 mg; 77% vs. 49%, P < .05, 95% CI 16.14–42.98), with similar systemic exposure.ConclusionsThe combinatorial tegoprazan in the IR and DR 1:1 ratio formulation was found to induce stronger gastric acid suppression throughout the day and at night, compared to the conventional IR formulation.