叶黄素微粒在中国健康受试者中的生物等效性研究  

Bioequivalence study of lutein beadlets in Chinese healthy subjects

作　　者：武峰[1] 赵秀丽[1] 郭韶洁[1] 倪四阳[1] 张莉华 许新德[3] WU Feng;ZHAO Xiu-li;GUO Shao-jie;NI Si-yang;ZHANG Li-hua;XU Xin-de(National Institute for Drug Clinical Trial,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China;Faculty of Food Science,Zhejiang Pharmaceutical College,Ningbo 315100,Zhejiang Province,China;Zhejiang Medicine Company Limited,Xinchang Pharma Factory,Shaoxing 312500,Zhejiang Province,China)

机构地区：[1]首都医科大学附属北京同仁医院国家药物临床试验机构,北京100730 [2]浙江医药高等专科学校食品学院,浙江宁波315100 [3]浙江医药股份有限公司新昌制药厂,浙江绍兴312500

出　　处：《中国临床药理学杂志》2022年第13期1522-1525,1534,共5页The Chinese Journal of Clinical Pharmacology

基　　金：“重大新药创制”国家科技重大专项基金资助项目(2011ZX09302-007-05)。

摘　　要：目的评价2种叶黄素微粒制剂在中国健康受试者体内的生物等效性及安全性。方法采用单中心、随机、开放、单次给药、两序列、两周期、双交叉设计,共入组30例中国健康成年男性受试者,在空腹条件下每周期分别单次口服叶黄素微粒的受试制剂或参比制剂20 mg。采用经确证的LC-MS/MS法测定血浆叶黄素浓度,使用WinNonlin软件按非房室模型计算药代动力学(PK)参数,并评价其生物等效性。结果受试制剂及参比制剂的主要PK参数如下:C_(max)分别为(275.84±108.66)和(303.30±148.60)ng·mL^(-1);T_(max)分别为(21.07±17.57)和(19.21±17.45)h;AUC_(0-72 h)分别为(14665.72±5278.20)和(16269.50±6853.12)ng·mL^(-1)·h。主要PK参数均值比的90%置信区间均在80.00%~125.00%,Tmax经非参数检验差异无统计学意义。试验期间共发生1例次不良事件,且与研究药物肯定无关。结论单次口服2种叶黄素微粒制剂具有生物等效性,口服叶黄素微粒安全性良好。Objective To investigate the bioequivalence and safety of two different lutein beadlets formulations in Chinese healthy subjects.Methods A single-center,randomized,open-label,single-dose,two sequences,two periods,crossover method was employed.Thirty Chinese male adult healthy subjects were enrolled and respectively administered 20 mg lutein beadlets test and reference formulations in oral single dose in fasting condition.Plasma lutein concentration was determined by a confirmed LC-MS/MS assay.The pharmacokinetic parameters were calculated and bioequivalence was assessed using WinNonlin software with non-compartment model.Results The main pharmacokinetic parameters of lutein beadlets test and reference formulations are respectively as follows:T_(max) were(21.07±17.57)and(19.21±17.45)h;C_(max) were(275.84±108.66)and(303.30±148.60)ng·mL^(-1);AUC_(0-72 h) were(14665.72±5278.20)and(16269.50±6853.12)ng·h·mL^(-1).The 90% confidential intervals of C_(max) and AUC for test formulation vs.reference formulation fall within 80.00%-125.00%.There is no statistically significant difference for T_(max) by non-parametric test.Totally 1 adverse event happened during the whole study,which was irrelevant with the study drug.Conclusion The two formulations of lutein beadlets are bioequivalent in oral single dose.Lutein beadlets shows good safety following oral administration.

关 键 词：叶黄素 液相色谱-质谱联用 药代动力学 生物等效性研究 

分 类 号：R969.4[医药卫生—药理学]