CLINICAL TRIAL Effect of food on the pharmacokinetics of YH4808, a potassium-competitive acid blocker, after single- and multiple-oral dosing in healthy subjects 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 Received: 4 April 2018 /Accepted: 31 May 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 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 Introduction Gastroesophageal reflux disease (GERD) is a representative acid-related disorder, in which the gastric contents reflux into the esophagus and cause symptoms such as heartburn, chest pain, regurgitation, and nausea [1]. Treatment for acid-related disorders has been advancing over the past decades [2]. The currently widely used agents, proton pump inhibitors (PPIs), are slow in onset of action and take several days to cause steady-state inhibition of the ATPase [2–5]. Moreover, PPIs do not sufficiently control nocturnal acid breakthrough, and their actions exhibit interpatient variability depending on the polymorphism of metabolic enzymes, especially for cyto- chrome P450 (CYP) 2C19 [6, 7]. Therefore, it is clear that there is an unmet medical need for treatment of acid-related disorders. Newer acid suppressants called potassium-competitive ac- id blockers (P-CABs) have been developed as an alternative treatment option to improve the treatment of these disorders [8]. P-CABs block gastric acid secretion reversibly by inhibiting the binding of K + to hydrogen potassium ATPase (H + /K + -ATPase). They are rapidly absorbed without the need for activation by the gastric acid, thereby exhibiting more * SeungHwan Lee leejh413@snu.ac.kr 1 Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea 2 Clinical Trial Center, Ajou University Medical Center, Suwon, Republic of Korea 3 Clinical Development Team, Yuhan Co. Ltd., Seoul, Republic of Korea 4 Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea European Journal of Clinical Pharmacology https://doi.org/10.1007/s00228-018-2502-9