YH4808 is a novel
potassium-competitive
acid blocker that is under clinical development to treat patients with
gastroesophageal reflux disease and
peptic ulcer diseases. In this study, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of
YH4808 were modeled in healthy male volunteers who received a single oral dose of
YH4808 at 30, 50, 100, 200, 400, 600, and 800 mg or matching placebo and multiple once-daily oral doses of
YH4808 at 100, 200, and 400 mg or matching placebo for 7 days. A population PK-PD model adequately described the time-concentration-effect profiles of
YH4808. The maximum increasing effect of
YH4808 on intragastric pH was 4.38, which was higher than the observed maximum increase in intragastric pH after
omeprazole at 40 mg (2.2 in pH). The maximum inhibitory effect by the increased intragastric pH on the exposure to repeated
YH4808 was 58% from baseline. Monte-Carlo simulation experiments based on the final model showed that
YH4808 at 200 mg will produce a higher percentage of time at pH > 4 over 24 h on day 1 than observed value of
esomeprazole at 40 mg once-daily, an active comparator (84.7% time vs. 58.3% time, respectively). Because
YH4808 at ≥200 mg resulted in a higher percentage of time at intragastric pH > 4 than seen after once-daily
esomeprazole at 40 mg and
YH4808 showed acceptable tolerability at a single-dose of 30-800 mg, we suggest to test the 200 mg once daily dosage regimen in further clinical trials of
YH4808.