Steady-State Pharmacokinetic Drug-Drug Interaction Study of Zastaprazan, a Novel Potassium-Competitive Acid Blocker, and Atorvastatin in Healthy Participants.
5 affiliations
- 1CHA Global Clinical Trial Center, CHA University Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.
- 2Department of Physiology, CHA University School of Medicine, Pocheon, Gyeonggi-do, Republic of Korea.
- 3Department of Pharmacology, School of Medicine, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
- 4Department of Clinical Pharmacology and Therapeutics, CHA University Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.
- 5Onconic Therapeutics Inc., Seoul, Republic of Korea.
Abstract
Purpose
Zastaprazan is a novel potassium-competitive acid blocker with CYP3A-mediated metabolism, whereas atorvastatin undergoes CYP3A4- and transporter-mediated disposition. Because these drugs may be co-administered and their net interaction cannot be inferred from shared metabolic pathways alone, this study evaluated their steady-state pharmacokinetic drug-drug interaction.Participants and methods
This open-label, fixed-sequence, three-period, multiple-dose study included healthy Korean men. Participants received atorvastatin 40 mg once daily, zastaprazan 20 mg once daily, and concomitant atorvastatin and zastaprazan, each for 5 consecutive days, under steady-state conditions. Plasma concentrations of zastaprazan, atorvastatin, and 2-hydroxyatorvastatin were measured, and geometric mean ratios (GMRs) with 90% confidence intervals (CIs) were calculated for C max,ss and AUC τ,ss.Results
Twenty-four healthy Korean men received at least one dose of a study drug, and 22 were included in the pharmacokinetic analysis. Atorvastatin decreased zastaprazan C max,ss by approximately 26% (GMR, 0.740; 90% CI, 0.655-0.836), whereas AUC τ,ss was preserved (GMR, 1.054; 90% CI, 0.927-1.198). Zastaprazan did not meaningfully alter atorvastatin exposure (C max,ss GMR, 0.982; 90% CI, 0.806-1.195; AUC τ,ss GMR, 1.029; 90% CI, 0.944-1.122). The AUC τ,ss of 2-hydroxyatorvastatin showed a modest decrease (GMR, 0.940; 90% CI, 0.889-0.994) that remained within the predefined conventional reference range. Co-administration was generally well tolerated, with no serious adverse events or adverse event-related discontinuations.Conclusion
Zastaprazan did not meaningfully alter atorvastatin C max,ss or AUC τ,ss under the studied conditions. Although atorvastatin reduced zastaprazan C max,ss, total exposure was preserved, a pattern consistent with altered absorption kinetics without establishing a specific mechanism. The pharmacodynamic significance of the lower zastaprazan C max,ss remains uncertain because intragastric pH was not measured. These pharmacokinetic findings do not suggest a need for atorvastatin dose adjustment under the studied conditions.
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BibTeX
@article{yang2026steadystate,
title = {{Steady-State Pharmacokinetic Drug-Drug Interaction Study of Zastaprazan, a Novel Potassium-Competitive Acid Blocker, and Atorvastatin in Healthy Participants.}},
author = {A-Young Yang and Hongsock Kim and Hyounggyoon Yoo and Yil-Seob Lee and John Kim and Wonsuk Shin},
journal = {Drug design, development and therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s647170},
url = {https://europepmc.org/article/MED/42921573},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Steady-State Pharmacokinetic Drug-Drug Interaction Study of Zastaprazan, a Novel Potassium-Competitive Acid Blocker, and Atorvastatin in Healthy Participants.
AU - A-Young Yang
AU - Hongsock Kim
AU - Hyounggyoon Yoo
AU - Yil-Seob Lee
AU - John Kim
AU - Wonsuk Shin
PY - 2026
DA - 2026/10/19
JO - Drug design, development and therapy
DO - 10.2147/dddt.s647170
UR - https://europepmc.org/article/MED/42921573
AB - Purpose Zastaprazan is a novel potassium-competitive acid blocker with CYP3A-mediated metabolism, whereas atorvastatin undergoes CYP3A4- and transporter-mediated disposition. Because these drugs may be co-administered and their net interaction cannot be inferred from shared metabolic pathways alone, this study evaluated their steady-state pharmacokinetic drug-drug interaction.Participants and methods This open-label, fixed-sequence, three-period, multiple-dose study included healthy Korean men. Participants received atorvastatin 40 mg once daily, zastaprazan 20 mg once daily, and concomitant atorvastatin and zastaprazan, each for 5 consecutive days, under steady-state conditions. Plasma concentrations of zastaprazan, atorvastatin, and 2-hydroxyatorvastatin were measured, and geometric mean ratios (GMRs) with 90% confidence intervals (CIs) were calculated for C max,ss and AUC τ,ss.Results Twenty-four healthy Korean men received at least one dose of a study drug, and 22 were included in the pharmacokinetic analysis. Atorvastatin decreased zastaprazan C max,ss by approximately 26% (GMR, 0.740; 90% CI, 0.655-0.836), whereas AUC τ,ss was preserved (GMR, 1.054; 90% CI, 0.927-1.198). Zastaprazan did not meaningfully alter atorvastatin exposure (C max,ss GMR, 0.982; 90% CI, 0.806-1.195; AUC τ,ss GMR, 1.029; 90% CI, 0.944-1.122). The AUC τ,ss of 2-hydroxyatorvastatin showed a modest decrease (GMR, 0.940; 90% CI, 0.889-0.994) that remained within the predefined conventional reference range. Co-administration was generally well tolerated, with no serious adverse events or adverse event-related discontinuations.Conclusion Zastaprazan did not meaningfully alter atorvastatin C max,ss or AUC τ,ss under the studied conditions. Although atorvastatin reduced zastaprazan C max,ss, total exposure was preserved, a pattern consistent with altered absorption kinetics without establishing a specific mechanism. The pharmacodynamic significance of the lower zastaprazan C max,ss remains uncertain because intragastric pH was not measured. These pharmacokinetic findings do not suggest a need for atorvastatin dose adjustment under the studied conditions.
SN - 1177-8881
ER -