Antiulcer drug - revaprazan

Despite the major advances in peptic ulcer treatment that took place with the introduction of the first H2 inhibitors cimetidine and ranitidine, plus the realisation that the bacterium Helicobacter pylori is probably responsible for the majority of ulcers, they remain a big health problem. The incidence of peptic ulcers and related conditions such as gastro-oesophageal reflux disease has risen over the years, and the cornerstone of treatment remains the use of acid-reducing drugs, both H2 inhibitors and the more recently introduced class, proton pump inhibitors (PPIs).

The earliest PPIs, such as omeprazole, have since been improved upon, with compounds with better pharmaco-kinetics and efficacy profiles. Yuhan Corp is investigating such a drug, revaprazan hydrochloride, formerly referred to as YH-1885. Unlike the first drugs in the class, it is a reversible inhibitor of H⁺K⁺-ATPase, and gives fewer adverse events than the irreversible inhibitors.

A Phase I study was carried out in 25 healthy male volunteers.¹ In the randomised double blind three way crossover study to investigate the drug's pharmacodynamics, subjects were given 100, 150 or 200mg orally once a day for three seven-day periods, separated by a seven day wash-out period. Significant inhibition of gastric acid secretion was seen, with the median intragastric pH of the three groups being 3.2, 3.9 and 4.2 respectively after the first seven days. The ability of revaprazan to suppress gastric acid secretion was negatively affected in those subjects who were infected with H. pylori bacteria.

A further trial was carried out in 46 healthy volunteers.² Subjects in the single blind randomised placebo-controlled dose rising parallel group study were randomly allocated to single doses of between 60 and 300mg or placebo, or to multiple dose groups of 150 and 300mg. The drug was given orally after overnight fasting, and dose-related pharmacological effects were obvious for dose groups of 150mg and higher in the single dose study. It was found to be safe and well tolerated.

A Phase II trial simulation has also been carried out.³ This was done using pharmacokinetic data from 52 subjects who were given five different doses of revaprazan, and intragastric pH information from 46 of these, taken at 48 to 72 hours after dosing. This showed that oral doses of 200 and 300mg, administered once a day before breakfast, could keep intragastric pH above 3 for around 20 hours, which is better than any currently available antiulcer drug. Phase III trials are now under way.