Absorption, Metabolism, and Excretion of [ 14 C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects

• Published in: Clinical pharmacology in drug development Vol. 13; no. 10; p. 1115
• Main Authors: Xie, Lijun, Xu, Yanjun, Liu, Wei, Zhou, Chen, Guo, Lian, Zhou, Sufeng, Zhang, Chen, Chen, Juan, Zhu, Bei, Ding, Sijia, Li, Huan, Zhang, Lingling, Wang, Li, Xu, Lingmei, Shao, Feng, Wang, Lu
• Format: Journal Article
• Language: English
• Published: United States 01.10.2024
• Subjects: Administration, Oral; Adult; Asian People; Carbon Radioisotopes; East Asian People; Feces - chemistry; Healthy Volunteers; Humans; Male; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - pharmacokinetics; Young Adult; proton pump inhibitors; metabolism; mass balance; anaprazole
• ISSN: 2160-7648
• DOI: 10.1002/cpdd.1458

Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20 mg/100 µCi of [ C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96 hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.