国产来那度胺胶囊的人体生物等效性临床研究

买佳佳; 丁艳华; 刘婷; 田海秋; 霍丹丹; 张英琪; 徐中南; 岳高超; 兰静; 梁文忠

doi:10.13201/j.issn.1004-2806.2019.01.007

国产来那度胺胶囊的人体生物等效性临床研究

- 1. 吉林大学第一医院(长春, 130021);
- 2. 正大天晴药业集团股份有限公司;
- 3. 上海药明康德新药开发有限公司

详细信息

通讯作者: 买佳佳,E-mail:2272135673@qq.com

中图分类号: R969.1

收稿日期: 2018-11-12

Bioequivalence of lenalidomide capsules in Chinese healthy volunteers

- 1. The First Bethune Hospital of Jilin University, Changchun, 130021, China;
- 2. Pharmaceutical Cttq Ltd.;
- 3. Shang Hai Wu Xi App Tec

More Information

Corresponding author: MAI Jiajia, E-mail: 2272135673@qq.com

Received Date: 12 November 2018

摘要

摘要: 目的:评价国产来那度胺胶囊在健康人体空腹/餐后状态下生物等效性试验研究。方法:采用开放、随机、两交叉、两周期试验设计,30例健康男性受试者随机分为2组,分别空腹/餐后口服受试制剂或参比制剂25 mg,0~24 h间隔采集血样。以液相色谱串联质谱法(LC-MS/MS)测定血浆来那度胺浓度,用WinNonlin软件计算药动学参数。结果:建立的LC-MS/MS法在1~1000 ng·mL^-1浓度范围内的线性关系良好,最低定量下限为1 ng·mL^-1,批间及批内精密度(RSD)均小于15%。空腹口服受试和参比制剂后,血浆中来那度胺的主要药动学参数如下:受试制剂和参比制剂的T_max分别为0.75[0.5,3]和0.75[0.5,2] h,C_max分别为(529.20±150.24)和(492.10±157.45) ng·mL^-1,t_1/2分别为(3.31±0.59)和(3.24±0.56) h,AUC_{0-24 h}分别为(1471.94±290.21)和(1446.96±289.91) h·ng·mL^-1。餐后口服受试和参比制剂后,受试制剂和参比制剂的T_max分别为3[0.5,4]和3[1.25,4] h,C_max分别为(248.77±65.71)和(241.57±55.40) ng·mL^-1,t_1/2分别为(3.57±0.45)和(3.62±0.42) h,AUC_{0-24 h}分别为(1227.55±285.04)和(1201.47±258.62) h·ng·mL^-1。结论:建立的LC-MS/MS法准确可靠,国产来那度胺胶囊和参比制剂瑞复美具有人体生物等效性。
- 国产来那度胺 /
- 生物等效性 /
- 液相色谱串联质谱法
Abstract: Objective:To investigate the bioequivalence of 2 formulations of lenalidomide capsules in Chinese healthy volunteers under fasting and postprandial conditions.Method:In a randomized two-way crossover study,30 healthy male volunteers were divided into two groups and were administrated orally with 25 mg of test or reference formulations under fasting and postprandial conditions.The blood samples were collected at several predetermined time intervals during 24 hours after administration.The plasma concentration of lenalidomide was determined by LC-MS/MS.The pharmacokinetic parameters were estimated using WinNonlin software.Result:The established LC-MS/MS method had linear calibration range over 1 to 1 000 ng·mL^-1 with a LLOQ (limit of quantitation) of 1 ng·mL^-1 for lenalidomide in human plasma.The inter- and intra-batch standard deviations were less than 15%.The pharmacokinetic parameters for the test and reference capsules under fasting conditions were as follows:T_max 0.75 [0.5,3] and 0.75 [0.5,2] h,C_max (529.20 ±150.24) and (492.10 ±157.45) ng·mL^-1,t_1/2 (3.31 ±0.59) and (3.24 ±0.56) h,AUC_{0-24 h} (1 471.94 ±290.21) and (1 446.96 ±289.91) h·ng·mL^-1.The pharmacokinetic parameters for the test and reference capsules under postprandial conditions were as follows:T_max 3 [0.5,4] and 3 [1.25,4] h,C_max (248.77±65.71) and (241.57±55.40) ng·mL^-1,t_1/2 (3.57±0.45) and (3.62±0.42) h,AUC_{0-24 h} (1 227.55±285.04) and (1 201.47±258.62) h·ng·mL^-1 respectively.Conclusion:The method is suitable for the pharmacokinetic study of lenalidomide capsules and the two preparations are bioequivalent.
- lenalidomide /
- bioequivalence /
- LC-MS/MS

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参考文献(5)

[1]	Lenalidomide, (REVLIMID?) specification, Celgene Corporation公司.Revised:02/2015.
[2]	国家食品药品监督管理总局.《药物临床试验质量管理规范》[S].2003.
[3]	国家食品药品监督管理局药品审评中心.生物等效性试验和等效性判断标准[S].2011.
[4]	Chen N, Weiss D, Reyes J, et al.No clinically significant drug interactions between lenalidomide and P-glycoprotein substrates and inhibitors:results from controlled phase I studies in healthy volunteers[J].Cancer Chemother Pharmacol, 2014, 73:1031-1039.
[5]	Weiss D, Knight R, Zhou S, et al.Evaluation of pharmacokinetic and pharmacodynamic interactions when lenalidomide is co-administered with warfarin in a randomized clinical trial setting[J].Clin Drug Investig, 2015, 35:455-461.