Pharmacokinetics, Metabolism, and Excretion of Licogliflozin, a Dual Inhibitor of SGLT1/2, in Rats, Dogs, and Humans
Creators: name: Wang-Lakshman, Lydia
name: Anisha E. Mendonza
name: Huber, Roland
name: Walles, Markus
name: He, YanLing
name: Venkateswar Jarugula
Publisher: name: Taylor & Francis
Year: 2021
Subjects: subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Physiology
subject: Pharmacology
subject: Evolutionary Biology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Ecology
subject: Marine Biology
subject: Cancer
subject: Inorganic Chemistry
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: Computational Biology

description: 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.Oral absorption of licogliflozin was rapid (t<sub>max</sub> &lt; 1 hr) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively.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%).The elimination of licogliflozin was predominantly via metabolism with 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 &gt;29% of the dose in excreta. Oxidative pathways were predominant in animal species. 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. Oral absorption of licogliflozin was rapid (t<sub>max</sub> &lt; 1 hr) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively. 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%). The elimination of licogliflozin was predominantly via metabolism with 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 &gt;29% of the dose in excreta. Oxidative pathways were predominant in animal species.