Daiichi Sankyo Pharma Development, Edison, New Jersey, USA.
Drug Metab Dispos. 2012 Dec;40(12):2250-5. doi: 10.1124/dmd.112.046888. Epub 2012 Aug 30.
This study determined the mass balance and pharmacokinetics of edoxaban in humans after oral administration of [¹⁴C]edoxaban. After oral administration of 60 mg (as active moiety) of [¹⁴C]edoxaban to six healthy male subjects, serial blood/plasma and urinary and fecal samples were collected for up to 168 h postdose. All samples were analyzed for total radioactivity by liquid scintillation counting and for concentrations of edoxaban and four metabolites in plasma, urine, and fecal samples by either high-performance liquid chromatography/tandem mass spectrometry method using multiple reaction modes, or a liquid chromatography radiometric method. The mean recovery of radioactivity was >97% of the administered radioactive dose, with 62.2% eliminated in feces and 35.4% in urine. Unchanged edoxaban accounted for the majority of radioactivity, with 49.1 and 23.8% of the dose as parent observed in feces and urine, respectively. Unchanged edoxaban was the most abundant species in plasma, with a mean area under the curve (AUC)(0-∞) of 1596 ng · h/ml. The next most abundant species was metabolite M4, with a mean AUC(0-∞) 147 ng · h/ml. The mass balance of edoxaban was well described, with unchanged edoxaban as the most abundant component of total radioactivity. Edoxaban is eliminated through multiple pathways, but each accounts for only a small amount of overall elimination.
本研究旨在确定人类口服[¹⁴C]依度沙班后依度沙班的物质平衡和药代动力学。6 名健康男性受试者口服 60mg（以有效部分计）[¹⁴C]依度沙班后，在给药后 168 小时内采集了一系列血/血浆和尿粪样本。所有样本均采用液体闪烁计数法检测总放射性，采用多反应模式的高效液相色谱/串联质谱法或放射性液相等效方法检测血浆、尿液和粪便样本中依度沙班和 4 种代谢物的浓度。放射性回收率平均>97%，其中 62.2%经粪便排泄，35.4%经尿液排泄。原形依度沙班占放射性物质的大部分，粪便和尿液中分别有 49.1%和 23.8%的剂量以原形药物排泄。原形依度沙班是血浆中丰度最高的物质，其 AUC(0-∞)为 1596ng·h/ml。丰度第二高的物质是代谢物 M4，其 AUC(0-∞)为 147ng·h/ml。依度沙班的物质平衡得到了很好的描述，原形依度沙班是总放射性中最主要的成分。依度沙班通过多种途径消除，但每种途径仅占总消除量的一小部分。
