注射用福沙匹坦双葡甲胺(150 mg)在中国健康受试者中单次给药的药代动力学研究

李洪涛; 何翠霞; 周焕; 汪华学

doi:10.16766/j.cnki.issn.1674-4152.003238

注射用福沙匹坦双葡甲胺(150 mg)在中国健康受试者中单次给药的药代动力学研究

doi: 10.16766/j.cnki.issn.1674-4152.003238

李洪涛¹,
何翠霞^{1, 2},
周焕^{1, 2},
汪华学^1, ,

1.
蚌埠医学院第一附属医院国家药物临床试验机构，安徽蚌埠 233004
2.
蚌埠医学院药学院，安徽蚌埠 233030

基金项目:

安徽高校自然科学重点研究项目 KJ2021A0815

安徽省生化药物工程技术研究中心开放研究基金 2023SYKFZ06

安徽省自然科学基金项目 2008085QH401

详细信息

通讯作者:
汪华学，E-mail: byyfywhx@163.com

中图分类号: R969.1 R975.4
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出版历程
- 收稿日期: 2022-12-11
- 网络出版日期: 2024-01-13

Pharmacokinetic study of single-dose fosaprepitant dimeglumine (150 mg) in healthy Chinese volunteers

LI Hongtao¹,
HE Cuixia^{1, 2},
ZHOU Huan^{1, 2},
WANG Huaxue^{1
, ,}

1.
Clinical Trials Center, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的研究中国健康受试者单剂量静脉输注由江苏奥赛康药业有限公司生产的注射用福沙匹坦双葡甲胺后的血药浓度经时变化，估算相应的药代动力学参数。同时，评估注射用福沙匹坦双葡甲胺在中国健康受试者中的安全性。方法本研究采用单中心、单剂量、单次给药的研究设计，空腹条件下入组12例受试者，每人静脉输注注射用福沙匹坦双葡甲胺150 mg，静滴时间为(30±2)min。使用液相色谱-串联质谱技术测定人血浆中福沙匹坦及其代谢产物阿瑞匹坦的浓度，采用Phoenix公司的WinNonlin6.4药动学软件进行药动学计算。结果健康受试者静脉滴注(30±2)min福沙匹坦双葡甲胺(150 mg)后，血浆中福沙匹坦迅速达峰并很快消除。其主要药动学参数如下：T_max为0.333 h；C_max为4.316 μg/mL；AUC_0-t为2.090 h·μg·mL^-1；AUC_0-∞为2.098 h·μg·mL^-1。福沙匹坦在体内迅速转化成阿瑞匹坦，其血药浓度在输注结束即达峰值。其主要药动学参数如下：T_max为0.583 h；C_max为4.888 μg/mL；AUC_0-t为49.483 h·μg·mL^-1；AUC_0-∞为54.658 h·μg·mL^-1。阿瑞匹坦在体内消除较慢，平均消除半衰期为19.3 h。血浆中阿瑞匹坦的暴露量远高于原形药物福沙匹坦，约为福沙匹坦的25.7倍。整个试验过程中，未发生非预期不良事件、严重不良事件和导致受试者退出的不良事件。结论单次静脉输注注射用福沙匹坦双葡甲胺(150 mg)后，福沙匹坦和阿瑞匹坦药代动力学参数与原研报道基本一致，在中国健康受试者中安全性良好。
- 注射用福沙匹坦双葡甲胺 /
- 阿瑞匹坦 /
- 液相色谱串联质谱 /
- 药代动力学 /
- 安全性
Abstract: Objective To study the time course of blood concentration after single-dose intravenous infusion of fosaprepitant dimeglumine for injection manufactured by Jiangsu Aosaikang Pharmaceutical Co., Ltd. in healthy Chinese subjects and to estimate the corresponding pharmacokinetic parameters. To evaluate the safety of fosaprepitant dimeglumine for injection in healthy Chinese subjects. Methods This was a single-centre, single-dose, single-dose study. Twelve subjects were enrolled under fasting conditions. Each of them received fosaprepitant dimeglumine for injection 150 mg for (30±2) min. The concentrations of fosaprepitant and its metabolite aprepitant in human plasma were determined by liquid chromatography tandem-mass spectrometry. WinNonlin6.4 pharmacokinetic software from Phoenix was used for pharmacokinetic calculation and SAS 9.4 for statistical analysis. Results In healthy volunteers, fosaprepitant dimeglumine (150 mg) was administered intravenously for (30±2) min and plasma fosaprepitant peaked and was rapidly cleared. The main pharmacokinetic parameters were as follows: T_max was 0.333 h; C_max was 4.316 μg/mL; AUC_0-t is 2.090 h·μg·mL^-1; AUC_0-∞ is 2.098 h·μg·mL^-1. Fosaprepitant is rapidly converted to aprepitant in the body and its blood concentration peaks at the end of the infusion. Key pharmacokinetic parameters were as follows: T_max was 0.583 h; C_max was 4.888 μg/mL; AUC_0-t was 49.483 h·μg·mL^-1; AUC_0-∞ was 54.658 h·μg·mL^-1. Aprepitant was slowly eliminated in vivo with a mean elimination half-life of 19.3 h. The plasma exposure of aprepitant was much higher than that of the originator drug fosaprepitant, approximately 25.7 times that of fosaprepitant. There were no unexpected adverse events, serious adverse events or adverse events leading to subject withdrawal throughout the study. Conclusion After a single intravenous infusion of fosaprepitant dimeglumine (150 mg) for injection, the pharmacokinetic parameters of fosaprepitant and aprepitant were consistent with those reported in the original research, and they were well tolerated in healthy Chinese volunteers.
- Fosaprepitant dimeglumine /
- Aprepitant /
- Liquid chromatography tandem-mass spectrometry /
- Pharmacokinetics /
- Safety

HTML全文

图 1 福沙匹坦的平均血药浓度-时间曲线

Figure 1. The mean blood concentration-time curve of fosaprepitant

下载: 全尺寸图片幻灯片

图 2 阿瑞匹坦的平均血药浓度-时间曲线

注：图A、B分别为阿瑞匹坦(0~72)h和(0~24)h的平均血药浓度-时间曲线。

Figure 2. The mean blood concentration-time curve of aprepitant

下载: 全尺寸图片幻灯片

表 1 福沙匹坦和阿瑞匹坦药物代谢动力学参数情况

Table 1. Pharmacokinetic parameters of fosaprepitant and aprepitant

组别	例数	t_1/2z (x±s，h)	T_max [M(min-max)，h]	C_max (x±s，μg/mL)	AUC_0-t (h·μg·mL^-1)	AUC_0-∞ (h·μg·mL^-1)	MRT_0-∞ (x±s，h)	CL (x±s，L/h)	V_ss (x±s，L)
福沙匹坦	12	0.037±0.005	0.333(0.167-0.500)	4.316±0.691	2.090±0.347	2.098±0.347	0.065±0.007	73.083±10.498	4.730±0.856
阿瑞匹坦	12	19.298±8.798	0.583(0.500-1.000)	4.888±1.448	49.483±15.177	54.658±21.359	25.767±10.864	/	/
注：T_max用中位数(最小值-最大值)表示。“/”为未计算相关数据。

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