Pharmacokinetics and safety study of single and multiple doses of icosapent ethyl in healthy Chinese subjects

doi:10.12092/j.issn.1009-2501.2026.08.007

Abstract

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

CLC Number:

R969.1

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.

Figures/Tables 4

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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