Bengbu Medical College, Bengbu, China.
Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Clin Pharmacol Drug Dev. 2021 Jul;10(7):748-755. doi: 10.1002/cpdd.892. Epub 2020 Dec 5.
Fosaprepitant dimeglumine (FD) is a precursor of aprepitant. FD can be metabolized into aprepitant. This randomized, single-center, open, 2-cycle, single-dose, crossover bioequivalence study compared the pharmacokinetics (PK) and safety of intravenously FD of test and reference products in healthy volunteers (HVs). HVs were assigned to the test group or reference group randomly and given FD intravenously. The plasma concentration of FD and aprepitant was measured using liquid chromatography-tandem mass spectrometry. PK parameters were ascertained based on a noncompartmental model. Data for 29 HVs were obtained. The geometric mean and 90% confidence intervals of maximum plasma concentration (C ), area under the concentration-time curve from time 0 to time of last measurable plasma concentration (AUC ), and area from the last datum point to time infinity (AUC ) of test and reference groups were 101.69% (95.06%, 108.77%), 103.52% (99.15%, 108.09%), and 105.58% (99.51%, 112.01%), respectively. These 3 parameters were within the acceptance range of 80.0% to 125.00%, and the test product was bioequivalent to the reference product. The coefficient of variation (CV) of C , AUC , and AUC was 15.14%, 9.67%, and 11.89%, respectively. Intravenously administered FD provided by 2 sponsors achieved bioequivalence. FD values from test and reference products were bioequivalent. All adverse events were mild and serious adverse events absent in HVs. This study indicated that FD may provide a safer alternative to aprepitant for chemotherapy-induced nausea and vomiting.
福沙匹坦双葡甲胺（FD）是阿瑞匹坦的前体药物。FD 可以代谢为阿瑞匹坦。这项随机、单中心、开放、2 周期、单剂量、交叉生物等效性研究比较了健康志愿者（HV）中受试和参比产品静脉注射 FD 的药代动力学（PK）和安全性。HV 随机分配到试验组或参比组，并静脉给予 FD。使用液相色谱-串联质谱法测定 FD 和阿瑞匹坦的血浆浓度。基于非房室模型确定 PK 参数。共获得 29 名 HV 的数据。试验组和参比组的最大血浆浓度（C ）、从 0 时间到最后可测量血浆浓度时间的浓度-时间曲线下面积（AUC ）和从最后数据点到无穷大的面积（AUC ）的几何均数和 90%置信区间分别为 101.69%（95.06%，108.77%）、103.52%（99.15%，108.09%）和 105.58%（99.51%，112.01%）。这 3 个参数均在 80.0%至 125.00%的可接受范围内，试验产品与参比产品具有生物等效性。C 、AUC 和 AUC 的变异系数（CV）分别为 15.14%、9.67%和 11.89%。2 个赞助商提供的静脉注射 FD 达到生物等效性。试验和参比产品的 FD 值具有生物等效性。所有不良事件均为轻度，HV 中无严重不良事件。本研究表明，FD 可能为化疗引起的恶心和呕吐提供一种比阿瑞匹坦更安全的替代药物。
