BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
Biopharm Drug Dispos. 2019 Jul;40(7):234-241. doi: 10.1002/bdd.2196. Epub 2019 Jul 19.
Loxoprofen is a prodrug that exerts strong analgesic and anti-inflammatory effects through its active trans-alcohol metabolite, which is produced in the liver by carbonyl reductase. Previous metabolic studies have evaluated loxoprofen, but its sulfate and taurine conjugates have not yet been studied. We characterized the metabolomic profile of loxoprofen in rat plasma, urine, and feces using high-resolution mass spectrometry. We identified 17 metabolites of loxoprofen in the three different biological matrices, 13 of which were detected in plasma and feces and 16 in urine. Amongst these metabolites, two novel taurine conjugates (M12 and M13) and two novel acyl glucuronides (M14, M15) were identified for the first time in rats. In addition, we detected three novel sulfate conjugates (M9, M10, and M11) of loxoprofen. Further study of these metabolites of loxoprofen is essential in order to assess their potency and toxicity.
洛索洛芬是一种前药，通过其在肝脏中由羰基还原酶产生的活性醇代谢物发挥强大的镇痛和抗炎作用。以前的代谢研究已经评估了洛索洛芬，但尚未研究其硫酸盐和牛磺酸缀合物。我们使用高分辨率质谱法在大鼠血浆、尿液和粪便中对洛索洛芬的代谢组学特征进行了表征。我们在三种不同的生物基质中鉴定了 17 种洛索洛芬的代谢物，其中 13 种在血浆和粪便中检测到，16 种在尿液中检测到。在这些代谢物中，首次在大鼠中鉴定出两种新的牛磺酸缀合物（M12 和 M13）和两种新的酰基葡萄糖醛酸缀合物（M14、M15）。此外，我们还检测到洛索洛芬的三种新的硫酸盐缀合物（M9、M10 和 M11）。进一步研究洛索洛芬的这些代谢物对于评估它们的效力和毒性至关重要。
