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OA

AIM:To evaluate the pharmacokinet-ics and safety of single and multiple doses of icos-apent 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,sub-jects received either 1 800 mg or 3 600 mg orally twice daily—immediately after breakfast and din-ner—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 Cmax were(11.79±3.27)(14.76±4.73)(15.51±7.84)µg/mL;the AUC0-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 AUC0-∞ were(1 792.93±927.10)(2 259.89±1 362.41)h·µg·mL-1,and(2 053.15±750.52)h·µg·mL-1,respectively.Following multiple oral dos-es of 1 800 mg and 3 600 mg,the Cmax,ss were(54.78±15.00)(83.35±22.11)µg/mL,and the AUCss 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 multi-ple doses.The dose-exposure relationship was non-linear,with plasma exposure to eicosapentaenoic acid increasing as the dose increased.