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European Journal of Clinical Pharmacology

, Volume 74, Issue 10, pp 1261–1272 | Cite as

Effect of food on the pharmacokinetics of YH4808, a potassium-competitive acid blocker, after single- and multiple-oral dosing in healthy subjects

  • Eunwoo Kim
  • Anhye Kim
  • Sojeong Yi
  • Yu Kyong Kim
  • Seong Bok Jang
  • Hae Mi Byun
  • Seo Hyun Yoon
  • Joo-Youn Cho
  • In-Jin Jang
  • Kyung-Sang Yu
  • SeungHwan LeeEmail author
Clinical Trial
  • 155 Downloads

Abstract

Purpose

YH4808 is a potassium-competitive acid blocker, developed for the treatment of acid-related disorders. Two clinical studies in healthy male subjects were conducted to evaluate the effect of food on the pharmacokinetics of YH4808.

Methods

The first study, a randomized, three-treatment, three-period, crossover study, compared pharmacokinetics of YH4808 (300 mg) after a single dose at fed state with a standard or a high-fat meal to those at fasted state. The second study, a randomized, two-treatment, two-period, crossover study, investigated pharmacokinetics at fasted or fed state with a standard meal after twice daily dose of YH4808 (100 mg) for 7 days. Bloods for pharmacokinetic evaluation were sampled up to 48 h post-dose and 24 h post-dose at steady state, respectively. The pharmacokinetic parameters were estimated by non-compartmental method.

Results

After single dosing, the geometric means of maximum plasma concentration increased by 1.2 and 2.1 times in the fed states with a standard meal and a high-fat meal, respectively, of that in fasted state. Corresponding values of area under the plasma concentration-time curve (AUC) from time 0 to the last measurable time point increased by 1.8 and 2.8 times, respectively. After multiple dosing, the geometric mean for 24-h AUC at steady state slightly increased in fed state by 1.1 times of that in fasted state.

Conclusions

As fat content of the food increased, the systemic exposure of YH4808 after single dosing increased. However, systemic exposures at steady state after multiple dosing between fasted and fed states were similar.

Trial registration

ClinicalTrials.gov registry no.: NCT01520012

Keywords

YH4808 Potassium competitive acid blocker Pharmacokinetics Food effect 

Notes

Funding information

This study was funded by Yuhan Co. Ltd., Seoul, Republic of Korea.

Compliance with ethical standards

The protocol was approved by the institutional review board of Seoul National University Hospital (SNUH). The studies were conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization guidelines. Written informed consents were obtained prior to enrolment in the studies.

Conflict of interest

The authors Seong Bok Jang and Hae Mi Byun are employees of Yuhan Co. Ltd. The first author (Eunwoo Kim) received a scholarship from the BK21-plus education program provided by the National Research Foundation of Korea. Sojeong Yi is currently employed by the U.S. Food and Drug Administration. Her contribution to the manuscript was based on her prior employment, and the current manuscript does not reflect any position of neither the U.S. Food and Drug Administration nor the US government. The authors have no other potential conflicts of interest to disclose regarding the content of this article.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Eunwoo Kim
    • 1
  • Anhye Kim
    • 2
  • Sojeong Yi
    • 1
  • Yu Kyong Kim
    • 1
  • Seong Bok Jang
    • 3
  • Hae Mi Byun
    • 3
  • Seo Hyun Yoon
    • 1
  • Joo-Youn Cho
    • 1
  • In-Jin Jang
    • 1
  • Kyung-Sang Yu
    • 1
  • SeungHwan Lee
    • 1
    • 4
    Email author
  1. 1.Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulRepublic of Korea
  2. 2.Clinical Trial CenterAjou University Medical CenterSuwonRepublic of Korea
  3. 3.Clinical Development TeamYuhan Co. Ltd.SeoulRepublic of Korea
  4. 4.Clinical Trials CenterSeoul National University HospitalSeoulRepublic of Korea

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