Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ, 08837, USA.
Clin Pharmacokinet. 2018 Feb;57(2):221-228. doi: 10.1007/s40262-017-0554-0.
Edoxaban is an orally active, direct factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation and for the treatment of venous thromboembolism.
This study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60-mg tablet crushed and administered via a nasogastric tube in a water suspension or orally mixed in apple puree.
This phase 1, open-label, crossover study randomized 30 healthy adults to receive three edoxaban treatment regimens (oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered via a nasogastric tube or orally in apple puree) in one of six treatment sequences.
Total edoxaban exposure was similar between the intact and crushed tablet regimens (mean area under the plasma concentration-time curve from time zero to infinity: whole tablet, 2132 ng·h/mL; nasogastric tube, 2021 ng·h/mL; apple puree, 2076 ng·h/mL). Mean maximum plasma concentration, area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, terminal half-life, and apparent total body clearance values were also similar. Time to maximum plasma concentration was significantly shorter for the nasogastric tube suspension and apple puree vs. the whole tablet [Hodges-Lehmann estimate of median difference (90% confidence interval): -0.75 (-1.25, -0.28); p = 0.0003 and -0.62 (-0.99, -0.26); p = 0.0024, respectively]. The maximum plasma concentation, area under the plasma concentration-time curve from time zero to infinity, and area under the plasma concentration-time curve from time zero to the time of the last measurable concentration were similar between treatment regimens; 90% confidence interval of the geometric least-squares means ratios were within the predefined 80-125% bioequivalence criterion. The safety and tolerability of edoxaban did not differ between treatment regimens.
The results support the use of edoxaban tablets crushed and administered either via a nasogastric tube or orally mixed in apple puree in patients who are unable to swallow solid oral dose formulations.
依度沙班是一种口服、直接的 Xa 因子抑制剂，适用于降低非瓣膜性心房颤动患者中风和全身性栓塞风险，也可用于治疗静脉血栓栓塞症。
本研究评估了依度沙班 60mg 片剂粉碎后混悬于水中经鼻胃管给药或与苹果泥混合后口服的药代动力学、安全性和耐受性。
这是一项开放标签、交叉的 1 期研究，将 30 名健康成年人随机分为三组，分别接受口服 60mg 依度沙班片剂、粉碎后经鼻胃管给药或与苹果泥混合后口服 60mg 依度沙班片剂的三种治疗方案，共涉及 6 种治疗顺序。
完整片剂和粉碎片剂方案的总依度沙班暴露量相似（零时刻至无穷大的血浆浓度-时间曲线下面积：整片给药，2132ng·h/mL；经鼻胃管给药，2021ng·h/mL；与苹果泥混合后口服，2076ng·h/mL）。最大血浆浓度、零时刻至最后一个可测量浓度的血浆浓度-时间曲线下面积、终末半衰期和表观总体清除率值也相似。与整片给药相比，经鼻胃管混悬液和与苹果泥混合后口服的达峰时间显著缩短[Hodges-Lehmann 估计的中位数差值（90%置信区间）：-0.75（-1.25，-0.28）；p=0.0003 和-0.62（-0.99，-0.26）；p=0.0024]。不同治疗方案的最大血浆浓度、零时刻至无穷大的血浆浓度-时间曲线下面积和零时刻至最后一个可测量浓度的血浆浓度-时间曲线下面积相似；几何均数比值的 90%置信区间均在预设的 80%~125%生物等效性范围内。不同治疗方案的依度沙班安全性和耐受性无差异。
研究结果支持无法吞咽固体制剂的患者使用粉碎后的依度沙班片剂经鼻胃管给药或与苹果泥混合后口服。
