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 (t_max < 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.

摘要：

1. 在男性大鼠，狗和健康的男性志愿者中研究了利格列净（一种钠-葡萄糖共转运蛋白（SGLTs）1和2抑制剂）的吸收，代谢和排泄（AME），并进行了报道。

2. 口服利格列净的吸收迅速（t _max <1小时），在大鼠，狗和人中的吸收分别为87％，100％和77％。

3. 口服利格列净相关放射性的排泄迅速而几乎完全，总放射性恢复率从狗的73％，人的92.5％到大鼠的100％不等。与尿素和粪便一起排泄与剂量有关的放射性，尿排泄在人类（〜56％）中比在动物物种（〜19-41％）中扮演更重要的角色。

4. 利格列净的消除主要是通过新陈代谢进行的，大部分放射性剂量（约54-74％）以代谢物的形式在物种间排泄。

5. 主要的生物转化途径涉及所有物种的直接葡萄糖醛酸化和氧化。在人类中，观察到的主要途径是直接葡萄糖醛酸化至M17和M27，约占排泄物剂量的38％，而氧化代谢也占排泄物剂量的29％以上。氧化途径在动物物种中占主导地位。