Summary Background Tegoprazan (CJ‐12420) is a potassium‐competitive acid blocker (P‐CAB) with therapeutic potential for gastro‐oesophageal reflux disease (GERD) by reversibly suppressing gastric H+/K+‐ATPase. Aims To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of tegoprazan Methods A phase I, randomised, double‐blind and placebo‐controlled clinical trial was conducted in 56 healthy male subjects without Helicobacter pylori infection. In the single ascending dose study, 50, 100, 200 and 400 mg tegoprazan were administered to 32 subjects. In the multiple ascending dose study, 100 and 200 mg tegoprazan were administered every 24 hours to each of the eight subjects for 7 days. In the comparative pharmacodynamics study, 40 mg esomeprazole was administered to eight subjects every 24 hours for 7 days. The assessment included safety, tolerability, pharmacodynamics through monitoring of 24‐hour gastric pH and pharmacokinetics of tegoprazan in plasma and urine. Results Tegoprazan was generally well tolerated. Most adverse events reported in the study were mild in intensity and resolved without any sequelae. Exposure to tegoprazan increased in a dose‐proportional manner. Multiple dosing with tegoprazan showed no accumulation in plasma on day 7. The pharmacodynamic analysis revealed that tegoprazan showed rapid, dose‐dependent gastric acid suppression. Conclusions Tegoprazan was well tolerated and showed rapid and potent gastric acid suppression. This supports the further development of tegoprazan as a treatment for acid‐related disorders.

SummaryBackgroundPotassium‐competitive acid blockers (P‐CABs) are emerging as novel treatments for acid‐related disorders including gastroesophageal reflux disease. Tegoprazan and revaprazan are approved P‐CABs in South Korea, but the pharmacodynamics and safety/tolerability of the two drugs have never been compared.AimsTo evaluate the pharmacodynamics and safety/tolerability of tegoprazan and revaprazan after single and multiple oral dosesMethodsA randomised, open‐label, active‐controlled study was conducted in Helicobacter pylori‐negative healthy Korean male subjects. Tegoprazan 50 mg or revaprazan 200 mg was administered orally, once daily for 7 days; 24‐h intragastric pH monitoring and serum gastrin were measured for pharmacodynamic evaluation. Safety parameters including serum microRNA‐122 (miR‐122) level were also collected.ResultsAfter a single dose, the %Time pH ≥4 for tegoprazan was greater than that for revaprazan (54.5% vs 25.1%). After multiple doses, the %Time pH ≥4 for tegoprazan was also greater than that for revaprazan (68.2% vs 25.3%). %Time pH ≥4 during 12 hours at nighttime for tegoprazan was greater than that for revaprazan (71.8% vs 31.9%). The changes in the serum gastrin were not clinically significant for either drug. Despite the slight increases of serum miR‐122 for each drug, tegoprazan and revaprazan were well tolerated considering other safety parameters including AST and ALT levels.ConclusionTegoprazan 50 mg showed stronger gastric acid suppression than revaorazan 200 mg. Both drugs were well tolerated.

No abstract

In this paper, we propose an efficient and simple fair queuing algorithm, called new starting potential fair queuing (NSPFQ), which has O(1) complexity for virtual time computation and also has good delay and fairness properties. NSPFQ introduces a simpler virtual time recalibration method as it follows a rate‐proportional property. The NSPFQ algorithm recalibrates the system virtual time to the minimum virtual start time among all possible virtual start times for head‐of‐line packets in backlogged sessions. Through analysis and simulation, we show that the proposed algorithm has good delay and fairness properties. We also propose a hardware implementation framework for the scheduling algorithm.

No abstract