二十碳五烯酸乙酯在中国健康受试者中单次、多次给药的药代动力学及安全性研究

doi:10.12092/j.issn.1009-2501.2026.08.007

摘要/Abstract

摘要：

目的: 评价单次和多次口服二十碳五烯酸乙酯软胶囊（商品名：EPADEL S^?）在中国健康成年男性受试者中的药代动力学及安全性。方法: 本研究采取单中心、开放设计。单次给药设3个剂量组（900、1 800、2 700 mg），受试者均于早餐后立即口服试验药物。多次给药设2个剂量组（1 800、3 600 mg），受试者分别于早餐后和晚餐后口服试验药物，每日给药2次，连续给药至第8天早餐后。各剂量组均纳入12例受试者。结果: 单次给药900、1 800、2 700 mg后：C_max分别为（11.79±3.27）、（14.76±4.73）、（15.51±7.84） μg/mL；AUC_0-t分别为（670.60±170.67）、（792.44±203.95）、（783.05±310.79） h·μg·mL^?1；AUC_0-∞分别为（1 792.93±927.10）、（2259.89±1362.41）、（2053.15±750.52） h·μg·mL^?1。多次给药1 800、3 600 mg后：C_{max, ss}分别为（54.78±15.00）、（83.35±22.11） μg/mL；AUC_ss分别为（570.50±162.14）、（848.85±192.14）h·μg·mL^?1。未发生严重不良事件和导致退出的不良事件，所有受试者耐受性良好。结论: 二十碳五烯酸乙酯在健康受试者单次和多次口服试验药物后安全性良好。比例化剂量暴露关系非线性，随着给药剂量的增加，血浆中二十碳五烯酸的暴露量增加。

关键词: 二十碳五烯酸乙酯, 中国健康受试者, 药代动力学

Abstract:

AIM: To evaluate the pharmacokinetics and safety of single and multiple doses of icosapent ethyl soft capsules (trade name: EPADEL S ^?）in healthy adult male Chinese subjects. METHODS: This study was a single-center, open-label trial. In the single-dose phase, subjects were assigned to one of three dose groups (900, 1 800 or 2 700 mg), with a single oral dose administered immediately after breakfast. In the multiple-dose phase, subjects received either 1 800 mg or 3 600 mg orally twice daily—immediately after breakfast and dinner—for a total of 8 days, ending with the morning dose on Day 8. Each dose group consisted of 12 subjects. RESULTS: Following single oral doses of 900, 1 800, and 2 700 mg, the corresponding C_max were (11.79±3.27) (14.76±4.73) (15.51±7.84) μg/mL; the AUC_0-t were (670.60±170.67) (792.44±203.95) h·μg·mL^?1 and (783.05±310.79) h·μg·mL^?1; and the AUC_0-∞ were (1792.93±927.10)(2259.89±1362.41) h·μg·mL^?1, and (2053.15±750.52) h·μg·mL^?1, respectively. Following multiple oral doses of 1 800 mg and 3 600 mg, the C_{max, ss} were (54.78±15.00) (83.35±22.11) μg/mL, and the AUC_ss were (570.50±162.14) and (848.85±192.14) h·μg·mL^?1, respectively. No serious adverse events or adverse events leading to withdrawal occurred, and all subjects had good tolerability. CONCLUSION: Icosapent ethyl exhibited a favorable safety profile in healthy subjects following both single and multiple doses. The dose–exposure relationship was nonlinear, with plasma exposure to eicosapentaenoic acid increasing as the dose increased.

Key words: icosapent ethyl, healthy Chinese subjects, pharmacokinetics

中图分类号:

R969.1

吴瑛, 许志玮, 李华芳, 沈一峰, 黄志伟, 李妍. 二十碳五烯酸乙酯在中国健康受试者中单次、多次给药的药代动力学及安全性研究[J]. 中国临床药理学与治疗学, 2026, 31(8): 1070-1075.

Ying WU, Zhiwei XU, Huafang LI, Yifeng SHEN, Zhiwei HUANG, Yan LI. Pharmacokinetics and safety study of single and multiple doses of icosapent ethyl in healthy Chinese subjects[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1070-1075.

图/表 4

参考文献 22

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Mean value (Mean±SD)	900 mg	1800 mg	2700 mg
C_max (μg/mL)	11.79±3.27	14.76±4.73	15.51±7.84
AUC_0-t (h·μg·mL^?1)	670.60±170.67	792.44±203.95	783.05±310.79
AUC_0-∞ (h·μg·mL^?1)	1792.93±927.10	2259.89±1362.41	2053.15±750.52
T_max (h)	21.47±24.35	14.94±12.06	13.32±5.58
t_1/2 (h)	100.57±48.39	104.14±76.27	98.30±54.55
MRT (h)	34.13±2.52	33.88±1.50	33.27±2.02
V_d/F (L)	75.65±15.36	118.31±32.13	190.91±66.21
CL/F (L/h)	0.63±0.33	1.01±0.44	1.50±0.60

Mean value (Mean±SD)	900 mg	1800 mg	2700 mg
C_max (μg/mL)	11.79±3.27	14.76±4.73	15.51±7.84
AUC_0-t (h·μg·mL^?1)	670.60±170.67	792.44±203.95	783.05±310.79
AUC_0-∞ (h·μg·mL^?1)	1792.93±927.10	2259.89±1362.41	2053.15±750.52
T_max (h)	21.47±24.35	14.94±12.06	13.32±5.58
t_1/2 (h)	100.57±48.39	104.14±76.27	98.30±54.55
MRT (h)	34.13±2.52	33.88±1.50	33.27±2.02
V_d/F (L)	75.65±15.36	118.31±32.13	190.91±66.21
CL/F (L/h)	0.63±0.33	1.01±0.44	1.50±0.60

PK parameters	Dose range	n	Estimated value of slope β₁	95%CI
C_max	900-2700 mg	12	0.22	(?3.12, 46.90)
AUC_0-t	900-2700 mg	12	0.13	(?8.16, 34.41)

PK parameters	Dose range	n	Estimated value of slope β₁	95%CI
C_max	900-2700 mg	12	0.22	(?3.12, 46.90)
AUC_0-t	900-2700 mg	12	0.13	(?8.16, 34.41)

Mean value (Mean±SD)	1800 mg (n=12)	3600 mg (n=11)
C_{max, ss} (μg/mL)	54.78±15.00	83.35±22.11
C_{min, ss} (μg/mL)	41.61±12.88	63.47±14.47
C_{ave, ss} (μg/mL)	47.54±13.51	70.74±16.01
AUC_ss (h·μg·mL^?1)	570.50±162.14	848.85±192.14
T_max (h)	2.16±3.23	0.54±1.78
t_1/2 (h)	40.46±8.07	33.47±3.19
CL_ss/F (h·μg·mL^?1)	1.72±0.54	2.24±0.57
DF (%)	28.94±10.98	27.32±9.19
Rac	5.38±0.97	4.55±0.38