Zastaprazan Disintegrating Tablet Matches Conventional Formulation Without Water

A new orally disintegrating tablet of zastaprazan produced nearly identical blood exposure to the conventional tablet in a randomized crossover trial, suggesting that patients may be able to take this fast-acting acid blocker without water. The study enrolled 54 healthy adult men and compared a 20 mg disintegrating tablet administered without water, the same tablet swallowed with water, and a conventional tablet taken with water. Plasma measurements showed that all three methods produced comparable absorption, peak drug levels and overall exposure, while no meaningful safety signals appeared with the new formulation.

Zastaprazan belongs to a relatively new class of medicines called potassium-competitive acid blockers, or P-CABs. Unlike proton pump inhibitors, which require specialized cellular mechanisms to suppress gastric acid, P-CABs act by blocking the potassium channel involved in acid secretion in the stomach’s parietal cells. The class has attracted interest because it can produce a faster and potentially longer-lasting rise in gastric pH than conventional acid suppression. Zastaprazan, developed in Korea, is already available as a standard tablet for acid-related disorders, including reflux esophagitis and peptic ulcer disease.

The new formulation was designed to disintegrate on the tongue, allowing it to be swallowed without water while an orange-flavored excipient improves palatability. Such dosage forms could offer practical advantages for people who have difficulty swallowing conventional tablets, including some older adults and patients with dysphagia, nausea or vomiting, or situations in which access to water is restricted. The trial also addressed a specific concern about disintegrating tablets: because the drug dissolves in the mouth, it might theoretically be absorbed through the buccal mucosa and enter the bloodstream faster than a tablet swallowed whole. The data did not show such an early exposure advantage.

Researchers conducted the open-label, randomized, single-dose study at the Biomedical Research Institute of H+ Yangji Hospital in South Korea. Participants were assigned in equal numbers to six treatment sequences, with each person receiving all three formulations in a different order. A one-week washout separated dosing periods, and all administrations occurred after an overnight fast under standardized conditions. Blood was sampled frequently during the first hours and then at intervals extending to 36 hours, allowing investigators to characterize both rapid absorption and the later elimination phase. Fifty-one participants completed all three periods; three withdrew after the first because of scheduling conflicts, and none left because of an adverse event.

Plasma concentrations of zastaprazan and its major circulating metabolite, M1, were measured with a validated liquid chromatography–tandem mass spectrometry method. The primary pharmacokinetic endpoints were maximum plasma concentration, or Cmax, and area under the concentration-time curve to the last measurable concentration, AUCt, which together describe systemic exposure. An analysis of variance on log-transformed values was used to calculate geometric mean ratios and 90% confidence intervals. Bioequivalence required all confidence intervals for these two primary measures to fall between 80% and 125% of the conventional tablet’s exposure, the standard acceptance range used in comparative bioavailability studies.

Both administration methods for the disintegrating tablet met that threshold. Without water, its Cmax was 95.05% of the conventional tablet, with a 90% confidence interval of 88.38% to 102.21%, while its AUCt was 108.00%, with an interval of 100.50% to 116.06%. When taken with water, the disintegrating tablet produced a Cmax ratio of 90.85%, with an interval of 84.96% to 97.16%, and an AUCt ratio of 101.88%, with an interval of 96.69% to 107.36%. The active metabolite M1 also had comparable exposure under both conditions, with its confidence intervals inside the same bioequivalence range. These results indicate that changing the dosage form did not materially alter how much zastaprazan reached the bloodstream or how quickly it was cleared.

The detailed absorption measures pointed in the same direction. Median time to peak concentration was 0.667 hours for the conventional tablet, 0.833 hours for the disintegrating tablet without water and 0.667 hours for the disintegrating tablet with water. Mean absorption rate constants were 1.41, 1.19 and 1.60, respectively, indicating no clinically meaningful formulation-related shift in absorption. The apparent elimination half-life was approximately nine hours across treatments, while apparent clearance and apparent volume of distribution were also similar. The investigators found no evidence of unusually rapid systemic entry after oral disintegration, including in an exploratory analysis of the active metabolite.

Safety monitoring found two mild treatment-related laboratory abnormalities in a single participant after the conventional tablet: one positive urine test for red blood cells and one for white blood cells. Neither was accompanied by symptoms, both were judged mild, and both resolved without specific treatment. No adverse drug reactions were reported after either administration of the disintegrating tablet, and no clinically meaningful changes were detected in vital signs, laboratory measures or electrocardiograms. The absence of new safety concerns is consistent with earlier healthy-volunteer data on conventional zastaprazan, which also reported no serious adverse events and only mild reactions such as headache and dyspepsia.

The findings support the disintegrating tablet as a potential alternative for people who cannot comfortably swallow a conventional tablet, but the trial’s design limits how broadly the result can be applied. It examined a single 20 mg dose in healthy young men under fasting conditions, rather than repeated dosing in older adults or patients with swallowing difficulty. People most likely to benefit may also have cancer, cardiovascular or cerebrovascular disease, and their conditions or concomitant medicines could affect drug absorption and safety. Research in the intended patient populations will therefore be needed to confirm that the formulation’s convenience translates into practical clinical benefit. Subject to that qualification, the study provides evidence that a water-free, orange-flavored version of zastaprazan can deliver the same systemic dose as the established conventional tablet without introducing a new safety signal.

Subject of Research: Pharmacokinetic bioequivalence and safety of orally disintegrating zastaprazan tablets in healthy adults

Article Title: Comparative Pharmacokinetics and Safety of Orally Disintegrating and Conventional Tablet Formulations of Zastaprazan in Healthy Subjects

Article References: Kim, H.-G., Kang, S., Min, S., Hong, H., & Bae, M. (2026). Comparative Pharmacokinetics and Safety of Orally Disintegrating and Conventional Tablet Formulations of Zastaprazan in Healthy Subjects. Pharmacology Research & Perspectives, 14(6), Article e70337. https://doi.org/10.1002/prp2.70337

Image Credits: AI Generated

DOI: 10.1002/prp2.70337

Keywords: zastaprazan, orally disintegrating tablets, bioequivalence, pharmacokinetics, acid suppression, potassium-competitive acid blockers, gastroesophageal reflux, drug formulation, clinical trials, patient adherence, Comparative, Safety