Evaluation of the comparative pharmacokinetic properties of a new orally disintegrating tablet of tegoprazan in healthy Korean subjects.

PURPOSE: Tegoprazan is a differentiated gastric acid-pump blocker and belongs to a class of potassium-competitive acid secretion blockers. An orally disintegrating tablet (ODT) of tegoprazan was developed to improve patient compliance. The purpose of this study was to compare pharmacokinetics (PK) and safety profiles between the conventional tablet (as the reference drug) and the ODT (as the test drug) of 50 mg tegoprazan in healthy Korean subjects. MATERIALS AND METHODS: An open-label, randomized, single-dose, 6-sequence, 3-period crossover study was conducted in 48 healthy subjects. All subjects received a single oral dose of tegoprazan 50 mg tablet with water, tegoprazan 50 mg ODT with water, and tegoprazan 50 mg ODT without water. Serial blood samples were collected up to 48 hours after dosing. Plasma concentrations of tegoprazan and its metabolite M1 were measured by LC-MS/MS, and PK parameters were calculated with a non-compartmental method. Safety was evaluated by means of assessed adverse events, physical examinations, laboratory test results as well as measurements of vital signs and ECG throughout the study. RESULTS: A total of 47 subjects completed the study. The 90% confidence intervals of the geometric mean ratios for AUCt, Cmax, and AUCinf of tegoprazan were 0.8873 - 0.9729, 0.8865 - 1.0569, and 0.8835 - 0.9695 for the test drug with water to the reference drug and 0.9169 - 1.0127, 0.9569 - 1.1276, and 0.9166 - 1.0131 for the test drug without water to the reference drug, respectively. There were no serious adverse events, and all adverse events were mild. CONCLUSION: The PK profiles of tegoprazan were equivalent between the conventional tablet and ODT with or without water. There was no significant difference in the safety profiles. Therefore, the novel ODT of tegoprazan that can be taken without water may improve compliance among patients with acid-related diseases.

Pharmacokinetics of a Fixed-Dose Combination of Teneligliptin Hydrochloride Hydrate and Modified-Release Metformin Under Fasting and Fed Conditions in Healthy Subjects.

Purpose: This study was performed to compare the pharmacokinetics of two fixed-dose combination (FDC) formulations of teneligliptin combined with modified-release metformin in healthy Korean subjects under fasting and fed conditions. Patients and Methods: The study was a single-center, open-label, single-dose, 2-way, 2-period, crossover trial. A total of 72 eligible subjects (40 subjects in the fasting state study and 32 subjects in the fed study) were enrolled in the study and were randomized to treatment. After the administration of a single FDC tablet of the investigational products, blood samples were collected at specific time intervals from 0 to 96 hours. The plasma concentrations of teneligliptin and metformin were measured by ultra performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios (test/reference) of the parameters were obtained through analysis of variance of the logarithmically transformed data. Results: The corresponding 90% CIs of area under the plasma concentration-time curve from time zero to the time of last measurable concentration (AUCt) and maximum plasma drug concentration (Cmax) for the test/reference geometric mean ratio (GMR) of teneligliptin were 94.81-101.32% and 86.03-97.63%, respectively, under fasting conditions. The corresponding 90% CIs of AUCt and Cmax for the test/reference GMR of metformin were 95.01-108.36% and 94.69-108.40%, respectively, under the fasting state and 98.82-107.56% and 97.25-106.99%, respectively, after feeding. All adverse events were of mild intensity, and the subjects recovered spontaneously without sequelae. Conclusion: The test FDC drug is equivalent to the reference FDC drug in subjects under fasting and fed conditions within the Korean regulatory bioequivalence criteria. Both formulations were safe and well tolerated, and there were no differences in the safety profiles between the two single FDC formulation drugs. Trial Registration No: Clinicaltrials.gov. KCT0007757, KCT0007759.