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Pharmacokinetics, Metabolism, and Excretion of Licogliflozin, a Dual Inhibitor of SGLT1/2, in Rats, Dogs, and Humans

Wang-Lakshman, Lydia and Mendonza, Anisha and Huber, Roland and Walles, Markus and He, Yan-Ling and Jarugula, Venkateswar (2021) Pharmacokinetics, Metabolism, and Excretion of Licogliflozin, a Dual Inhibitor of SGLT1/2, in Rats, Dogs, and Humans. Xenobiotica.

Abstract

1. The 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 hr) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively.
3. The 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. The elimination of licogliflozin was predominantly via metabolism with 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.

Item Type: Article
Keywords: SGLT1/2 inhibitor, AME, biotransformation, glucuronidation, oxidative metabolism
Date Deposited: 26 Jan 2021 00:45
Last Modified: 26 Jan 2021 00:45
URI: https://oak.novartis.com/id/eprint/43236

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