Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 51, 2021 - Issue 4
234
Views
5
CrossRef citations to date
0
Altmetric
Clinical Pharmacokinetics and Metabolism

Pharmacokinetics, metabolism, and excretion of licogliflozin, a dual inhibitor of SGLT1/2, in rats, dogs, and humans

, , , , &
Pages 413-426 | Received 04 Nov 2020, Accepted 17 Dec 2020, Published online: 12 Jan 2021
 

Abstract

  1. Absorption, metabolism, and excretion (AME) of licogliflozin, a sodium-glucose co-transporters (SGLTs) 1 and 2 inhibitor, were studied in male rats, dogs, and healthy male volunteers and reported.

  2. Oral absorption of licogliflozin was rapid (tmax < 1 h) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively.

  3. Excretion of licogliflozin-related radioactivity was rapid and nearly complete following oral administration with total radioactivity recovery ranging from 73% in dogs, 92.5% in humans, to 100% in rats. Dose-related radioactivity was excreted in both urine and faeces with urinary excretion playing a slightly more important role in humans (∼56%) than in animal species (∼19–41%).

  4. Elimination of licogliflozin was predominantly via metabolism with the majority of the radioactivity dose (∼54–74%) excreted as metabolites across species.

  5. The principal biotransformation pathways involved direct glucuronidation and oxidation across all species. In humans, direct glucuronidation to M17 and M27 was the major pathway observed, accounting for ∼38% of the dose in excreta while oxidative metabolism also contributed to >29% of the dose in excreta. Oxidative pathways were predominant in animal species.

Disclosure statement

The authors report no potential conflict of interest.

Additional information

Funding

This work was supported by the Novartis Institutes of BioMedical Research.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.