来那度胺胶囊单次空腹及餐后状态下给药在健康受试者的生物等效性研究  

Bioequivalence of lenalidomide capsule after a single oral dose in fasting and postprandial healthy volunteers

作　　者：孙明媛 郑维维 姜波 朱海玲 张望 崔岩 倪钰峰 陈昱竹 杨雪 韩盈 贾仕玲 齐军元 SUN Ming-yuan;ZHENG Wei-wei;JIANG Bo;ZHU Hai-ling;ZHANG Wang;CUI Yan;NI Yu-feng;CHEN Yu-zhu;YANG Xue;HAN Ying;JIA Shi-ling;QI Jun-yuan(Phase I Clinical Trail Unit,State Key Laboratory of Experimental Hematology,National Clinical Research Center for Hematological Disorders,Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300020,China;Beijing HaiSha Consulting Co.,LTD,Beijing 100044,China;Labcorp Shanghai Bioanalytical Lab,Shanghai 201203,China)

机构地区：[1]中国医学科学院血液病医院、中国医学科学院血液学研究所,实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,Ⅰ期临床研究病房,天津300020 [2]北京海莎咨询有限公司,北京100044 [3]Labcorp上海生物分析实验室,上海201203

出　　处：《中国临床药理学杂志》2022年第8期837-841,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(2017ZX09304024)。

摘　　要：目的评估2种来那度胺胶囊25 mg在中国男性健康受试者中的生物等效性。方法本研究包括空腹和餐后2个试验,均用随机、开放、两周期、两交叉试验设计。空腹试验入组24例、餐后试验入组30例健康男性受试者,随机、交叉单次口服受试和参比来那度胺胶囊25 mg,用HPLC-MS/MS法测定血浆中来那度胺的血药浓度,根据非房室模型用Phoenix WinNonlin 6.4软件计算两者的药代动力学参数,用SAS 9.4软件进行生物等效性评价。结果在空腹状态下,受试者单剂量口服受试和参比来那度胺胶囊25 mg后,主要药代动力学参数:C_(max)分别为(615.00±165.00)和(569.00±118.00)ng·mL^(-1),AUC_(0-t)分别为(1512.00±158.00)和(1532.00±183.00)ng·mL^(-1)·h,AUC_(0-∞)分别为(1519.00±159.00)和(1539.00±185.00)ng·mL^(-1)·h;在餐后状态下,受试者单剂量口服受试和参比来那度胺胶囊25 mg后,主要药代动力学参数:C_(max)分别为(262.00±50.60)和(244.00±50.60)ng·mL^(-1),AUC_(0-t)分别为(1325.00±158.00)和(1265.00±212.00)ng·mL^(-1)·h,AUC_(0-∞)分别为(1343.00±161.00)和(1282.00±215.00)ng·mL^(-1)·h。在空腹状态下,两制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)经对数转换后几何均值比值的90%置信区间分别为96.26%~118.58%,96.02%~101.72%和96.03%~101.70%,在餐后状态下,分别为99.86%~116.13%,101.25%~109.74%和101.35%~109.70%。结论2种来那度胺胶囊具有生物等效性。Objective To evaluate the bioequivalence of the two 25 mg lenalidomide capsules in healthy Chinese male volunteers.Methods This was a randomized,open-label,two-period,cross-over pharmacokinetic study in healthy Chinese male volunteers under fast and fed conditions.A total of 24 subjects in fasting state and 30 subjects in fed state were given single oral dose of 25 mg test and reference lenalidomide capsules respectively.The concentrations of lenadomide in plasma were determined by HPLC-MS/MS.The pharmacokinetic paramters were calculated by non-compartment model of Phoenix WinNonlin 6.4,and the bioequivalence was evaluated by SAS 9.4.Results The pharmacokinetic paramters after a single oral administration of 25 mg test and reference formulations in fasting state were as follows:C_(max) were(615.00±165.00)and(569.00±118.00)ng·mL^(-1),AUC_(0-t) were(1512.00±158.00)and(1532.00±183.00)ng·mL^(-1)·h,AUC_(0-∞) were(1519.00±159.00)and(1539.00±185.00)ng·mL^(-1)·h,respectively.The pharmacokinetic paramters after a single oral administration of 25 mg test and reference formulations in fed state were as follows:C_(max) were(262.00±50.60)and(244.00±50.60)ng·mL^(-1),AUC_(0-t) were(1325.00±158.00)and(1265.00±212.00)ng·mL^(-1)·h,AUC_(0-∞) were(1343.00±161.00)and(1282.00±215.00)ng·mL^(-1)·h,respectively.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t) and AUC_(0-∞) after logarithmic conversion were respectively 96.26%-118.58%,96.02%-101.72%and 96.03%-101.70%in fasting state,99.86%-116.13%,101.25%-109.74%and 101.35%-109.70%in fed state.Both formulations were well tolerated.Conclusion The test and reference lenalidomide capsules were bioequivalent.

关 键 词：来那度胺胶囊 生物等效性 高效液相色谱-质谱联用 

分 类 号：R979.1[医药卫生—药品]