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
Autor: | H. M. Byun, Sumin Yoon, Kyung Sang Yu, Jang Ij, Howard Lee, Jai Young Cho, Sojeong Yi, S. B. Jang |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male Pharmacology Placebo 030226 pharmacology & pharmacy Esomeprazole Gastric Acid Young Adult 03 medical and health sciences 0302 clinical medicine Double-Blind Method Pharmacokinetics medicine Humans Pharmacology (medical) Cross-Over Studies Hepatology business.industry Gastroenterology Hydrogen-Ion Concentration Anti-Ulcer Agents Crossover study Regimen Tolerability Pharmacodynamics Gastric acid 030211 gastroenterology & hepatology business medicine.drug |
Zdroj: | Alimentary Pharmacology & Therapeutics. 46:337-346 |
ISSN: | 0269-2813 |
Popis: | SummaryBackground YH4808, a K+-competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease. Aims We aimed to determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. Methods This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). Results Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered. Conclusion This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases. |
Databáze: | OpenAIRE |
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