Effect of food on the pharmacokinetics of YH4808, a potassium-competitive acid blocker, after single- and multiple-oral dosing in healthy subjects
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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.
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.
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.
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.
ClinicalTrials.gov registry no.: NCT01520012
KeywordsYH4808 Potassium competitive acid blocker Pharmacokinetics Food effect
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.
- 3.Satoh K, Yoshino J, Akamatsu T, Itoh T, Kato M, Kamada T, Takagi A, Chiba T, Nomura S, Mizokami Y, Murakami K, Sakamoto C, Hiraishi H, Ichinose M, Uemura N, Goto H, Joh T, Miwa H, Sugano K, Shimosegawa T (2016) Evidence-based clinical practice guidelines for peptic ulcer disease 2015. J Gastroenterol 51(3):177–194CrossRefPubMedGoogle Scholar
- 11.Yuhan Co. Ltd. S. YH4808 Investigator Brochure (Ver 11.0). 2013. UnpublishedGoogle Scholar
- 12.Yi S, Lee H, Jang SB, Byun HM, Yoon SH, Cho JY, Jang IJ, Yu KS (2017) A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers. Aliment Pharmacol Ther 46:337–346CrossRefPubMedGoogle Scholar
- 13.KIST (Korea Institute of Science and Technology). ADME study of YH4808 using isotope (Yuhan Co. Ltd., Seoul). 2008. UnpublishedGoogle Scholar
- 15.U.S. Department of Health and Human Services. Food and Drug Administration (FDA). Center for Drug Evaluation and Research (CDER). Guidance for industry: food-effect bioavailability and fed bioequivalence Studies 2002Google Scholar
- 16.Rowland M, Tozer TN (2010) Clinical pharmacokinetics and pharmacodynamics: concepts and applications, 4th edn. Wolters Kluwer Health/Lippincott William & Wilkins, Philadelphia, p 184Google Scholar
- 19.Lee PID, Amidon GL (1996) Pharmacokinetic analysis: a practical approach. CRC Press, Boca Raton, p 324Google Scholar