Myeongjoong Kim

Korea Innotech (South Korea)

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Geun Seog Song

Korea Innotech (South Korea)

Bongtae Kim

Korea Innotech (South Korea)

Kenneth A. Jacobson

National Institute of Diabetes and Digestive and Kidney Diseases

In‐Jin Jang

Seoul National University Hospital

Minyoung Noh

California State University Los Angeles

Dong‐Hyun Kim

Konkuk University

So-young Jung

Daegu-Gyeongbuk Medical Innovation Foundation

Xiyan Hou

Dalian Minzu University

Su Chul Lee

Kyungpook National University

Shi Hyang Lee

University of Ulsan

Cooperative Institutions

Seoul National University

Korea Innotech (South Korea)

New Generation University College

Seoul National University Hospital

National University College

National Institute of Diabetes and Digestive and Kidney Diseases

National Institutes of Health

Asan Medical Center

Yonsei University

Kyung Hee University

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Development of a patient-centric formulation of tegoprazan, a novel potassium-competitive acid blocker, using modified-release drug-coated pellets

Journal of Pharmaceutical Investigation (2022)

Su Chul Lee Myeongjoong Kim Dong‐Hyun Kim Eun Kyung Jeon Eun Hee Lee

Capsule

Enteric coating

10.1007/s40005-022-00582-y

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Citations (2)

External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long‐chain triglyceride emulsion propofol in beagle dogs

Journal of Veterinary Pharmacology and Therapeutics (2011)

Shi Hyang Lee Hyun‐Mee Park Myeongjoong Kim Minyoung Noh Hee-Suk Yoon

This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.

Beagle

Pharmacodynamics

Crossover study

Approximate entropy

Microemulsion

10.1111/j.1365-2885.2011.01321.x

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Citations (13)

Structural Modification and Biological Evaluation of 2,8-Disubstituted Adenine and Its Nucleosides as A_2A Adenosine Receptor Antagonists: Exploring the Roles of Ribose at Adenosine Receptors

Journal of Medicinal Chemistry (2024)

Gibae Kim Dnyandev B. Jarhad Grim Lee Gyudong Kim Xiyan Hou

Building on the preceding structural analysis and a structure–activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hA2AAR. Among the synthesized derivatives, 2-aryl-8-hexynyl adenine 4a demonstrated the highest selectivity for hA2AAR (Ki,hA2A = 5.0 ± 0.5 nM, Ki,hA3/Ki,hA2A = 86) and effectively blocked cAMP production and restored IL-2 secretion in PBMCs. Favorable pharmacokinetic properties and a notable enhancement of anticancer effects in combination with an mAb immune checkpoint blockade were observed upon oral administration of 4a. These findings establish 4a as a viable immune-oncology therapeutic candidate.

Ribose

10.1021/acs.jmedchem.4c01003

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Carcinogenicity assessment of tegoprazan in Sprague-Dawley (Crl:CD) rats and ICR (Crl:CD1) mice

Regulatory Toxicology and Pharmacology (2023)

Myeongjoong Kim Bongtae Kim Ju‐Hyun Lee Dong‐Hyun Kim Geun Seog Song

Enterochromaffin-like cell

Enterochromaffin cell

Granular cell

10.1016/j.yrtph.2023.105424

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Citations (2)

Prediction of Drug–Drug Interaction Potential of Tegoprazan Using Physiologically Based Pharmacokinetic Modeling and Simulation

Pharmaceutics (2021)

Deok Yong Yoon SeungHwan Lee In‐Jin Jang Myeongjoong Kim Heechan Lee

This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of tegoprazan and to predict the drug–drug interaction (DDI) potential between tegoprazan and cytochrome P450 (CYP) 3A4 perpetrators. The PBPK model of tegoprazan was developed using SimCYP Simulator® and verified by comparing the model-predicted pharmacokinetics (PKs) of tegoprazan with the observed data from phase 1 clinical studies, including DDI studies. DDIs between tegoprazan and three CYP3A4 perpetrators were predicted by simulating the difference in tegoprazan exposure with and without perpetrators, after multiple dosing for a clinically used dose range. The final PBPK model adequately predicted the biphasic distribution profiles of tegoprazan and DDI between tegoprazan and clarithromycin. All ratios of the predicted-to-observed PK parameters were between 0.5 and 2.0. In DDI simulation, systemic exposure to tegoprazan was expected to increase about threefold when co-administered with the maximum recommended dose of clarithromycin or ketoconazole. Meanwhile, tegoprazan exposure was expected to decrease to ~30% when rifampicin was co-administered. Based on the simulation by the PBPK model, it is suggested that the DDI potential be considered when tegoprazan is used with CYP3A4 perpetrator, as the acid suppression effect of tegoprazan is known to be associated with systemic exposure.

Drug-drug interaction

10.3390/pharmaceutics13091489

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Citations (12)