Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
BioCore Co., Ltd., Seoul, Korea.
Clin Transl Sci. 2021 Jan;14(1):231-238. doi: 10.1111/cts.12848. Epub 2020 Sep 26.
The absorption, metabolism, and excretion (AME) profiles of KD101, currently under clinical development to treat obesity, were assessed in humans using accelerator mass spectrometry (AMS) after a single oral administration of KD101 at 400 mg and a microdose of C-KD101 at ~ 35.2 μg with a total radioactivity of 6.81 kBq. The mean total recovery of administered radioactivity was 85.2% with predominant excretion in the urine (78.0%). The radio-chromatographic metabolite profiling showed that most of the total radioactivity in the plasma and the urine was ascribable to metabolites. The UDP-glucuronosyltransferase (UGT), including UGT1A1, UGT1A3, and UGT2B7, might have contributed to the interindividual variability in the metabolism and excretion of KD101. The microtracing approach using AMS is a useful tool to evaluate the AME of a drug under development without risk for high radiation exposure to humans.
使用加速器质谱法（AMS）评估了正在开发中的用于治疗肥胖症的 KD101 的吸收、代谢和排泄（AME）特征。在单次口服 400mg KD101 和约 35.2μg 的 C-KD101 微剂量后，总放射性为 6.81kBq。给予放射性的平均总回收率为 85.2%，主要以尿液形式排泄（78.0%）。放射性色谱代谢物分析表明，血浆和尿液中大部分总放射性归因于代谢物。UDP-葡糖醛酸基转移酶（UGT），包括 UGT1A1、UGT1A3 和 UGT2B7，可能导致 KD101 的代谢和排泄个体间差异。使用 AMS 的微量追踪方法是一种有用的工具，可用于评估开发中的药物的 AME，而不会对人体产生高辐射暴露的风险。
