Pharmacokinetics, mass balance, and metabolism of the novel potassium-competitive acid blocker JP-1366 in healthy Chinese adults following a single oral dose of [14C]JP-1366

Introduction JP-1366 (zastaprazan), a novel potassium-competitive acid blocker (P-CAB), was approved in South Korea in 2024 for treating erosive gastroesophageal reflux disease (GERD). This mass balance study characterized the pharmacokinetics, metabolism, excretion, and safety profile of JP-1366 in humans, supporting its further clinical development in China. Methods Six healthy Chinese male adults received a single oral dose of 20 mg (100 μCi) [ 14 C]JP-1366 under fasting conditions in this open-label Phase I study. Serial samples of blood, plasma, urine, and feces were collected and analyzed to determine Pharmacokinetic parameters, total radioactive recovery, metabolic fate, and excretion routes. Results JP-1366 was rapidly absorbed, with median T max values of 0.875 h observed for both the parent drug and total radioactivity in human plasma. The mean plasma elimination half-life (t 1/2 ) was approximately 28 h for JP-1366-related material. Furthermore, the blood-to-plasma ratio of total radioactivity ranged from 0.561 to 0.645, indicating limited distribution of drug-related material into blood cells. Within 264 h post-dose, 94.3% of the administered radioactive dose was recovered through excretion, predominantly via feces (51.9%) and urine (42.4%). JP-1366 underwent extensive metabolism in vivo , generating 57 metabolites, while the parent drug remained undetectable in excreted samples. The principal metabolic pathways involved oxidations (Phase I) and the following glucuronidation (Phase I/II). JP-1366 exhibited a favorable safety profile, with no serious adverse events reported. Conclusion JP-1366 exhibited favorable pharmacokinetic properties characterized by rapid absorption, extensive metabolism, and predominant fecal excretion of drug-related material. The principal metabolic pathways involved oxidations and the following glucuronidation. Clinical Trial Registration http://www.chinadrugtrials.org.cn/ , identifier CTR20244931.