Pharmacokinetics, metabolism, and excretion of licogliflozin, a dual inhibitor of SGLT1/2, in rats, dogs, and humans
Journal Type: Journal Paper
Journal: Xenobiotica 2021 Apr;51(4):413-426, doi: 10.1080/00498254.2020.1867331
Pubmed: 33413022
Impact Factor: 1.902
Date of Acceptance: 17 Dec 2020
- 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.
- Oral absorption of licogliflozin was rapid (tmax < 1 h) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively.
- 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%).
- Elimination of licogliflozin was predominantly via metabolism with the majority of the radioactivity dose (∼54–74%) excreted as metabolites across species.
- 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.