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Xenobiotica
the fate of foreign compounds in biological systems
Volume 48, 2018 - Issue 10
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Clinical Pharmacokinetics and Metabolism

Mass balance and metabolism of Z-215, a novel proton pump inhibitor, in healthy volunteers

, , , , , , & show all
Pages 1006-1020 | Received 30 Aug 2017, Accepted 06 Oct 2017, Published online: 02 Nov 2017
 

Abstract

The human mass balance of [14 C]Z-215, a novel proton pump inhibitor, was characterised in six healthy male volunteers following single oral administration of [14 C]Z-215 (20 mg, 3.7 MBq) to determine the elimination pathway of Z-215 and the distribution of its metabolites in plasma, urine, and faeces (NCT02618629). [14 C]Z-215 was rapidly absorbed, with a Cmax of 434 ng/mL at 0.38 h for Z-215 and 732 ng eq./mL at 0.5 h for total radioactivity. Means of 59.61% and 31.36% of the administered radioactive dose were excreted in urine and faeces, respectively, within 168 h post-dose. The majority of the dose was recovered within 24 h in urine and 96 h in faeces. Unchanged Z-215 was excreted in urine at trace levels but was not detected in faeces. The main components in plasma were Z-215 and Z-215 sulphone, accounting for 29.8% and 13.3% of the total circulating radioactivity, respectively. Additionally, Z-215 was metabolised through oxidation, reduction and conjugation. Our in vitro Z-215 metabolism study showed that the major isozyme contributing to the oxidation of Z-215, including the formation of Z-215 sulphone, was CYP3A4. In conclusion, Z-215 is well absorbed in humans and primarily eliminated via metabolism, where CYP3A4 plays an important role.

Declaration of interest

All authors are employees of Zeria Pharmaceutical Co., Ltd. The authors declare no other conflicts of interests.

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