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Outline
To evaluate the excretion pathway, pharmacokinetic properties, and cardiac safety of the dipeptidyl peptidase-4 (DPP-4) inhibitor LGT-6 in rats, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to determine drug concentrations in biological samples, in combination with an automated patch-clamp technique (automated patch clamp, APC) to assess the risk of human ether-à-go-go-related gene (hERG) potassium channel inhibition. The results showed that LGT-6 is primarily excreted via the biliary route in rats, with a cumulative excretion rate of approximately 82.4%. Following single-dose administration via tail vein injection (5 mg·kg-1) or oral gavage (5 mg·kg-1), the absolute bioavailability of LGT-6 was 77.2%. The IC50 of LGT-6 against the hERG potassium channel was greater than 30 μmol·L-1. The analytical methods established in this project for quantifying various target components in in vivo and in vitro biological samples all complied with relevant regulatory technical requirements. These data indicate that LGT-6 exhibits absorption, distribution, metabolism, and excretion (ADME) characteristics dominated by biliary excretion and high oral absorption efficiency, along with a low cardiac safety risk, thereby providing key experimental evidence to support its further preclinical safety evaluation and subsequent development. This experiment was approved by the Animal Ethics Committee of Guizhou Medical University (Grant No: 1900912).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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