健康受试者餐后口服不同剂型比卡鲁胺的生物等效性研究  

Bioequivalence study of bicalutamide in different formulations after high-fat meal in healthy volunteers

作　　者：张浩[1,2] 张文萍[1,2] 张宇馨[1,2] 马妍妮[1,2] 贺少龙 杨小英[1,2] ZHANG Hao;ZHANG Wen-ping;ZHANG Yu-xin;MA Yan-ni;HE Shao-long;YANG Xiao-ying(Department of Pharmacy,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China;Division of Clinical Pharmacology,General Hospital of Ningxia Medical University,Yinchuan 750004,Ningxia Hui Autonomous Region,China)

机构地区：[1]宁夏医科大学总医院药剂科,宁夏回族自治区银川750004 [2]宁夏医科大学总医院临床药理研究室,宁夏回族自治区银川750004

出　　处：《中国临床药理学杂志》2023年第5期728-732,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价中国健康男性受试者餐后口服比卡鲁胺胶囊(受试制剂)或比卡鲁胺片(参比制剂)的生物等效性与安全性。方法单中心、平行、两制剂、单剂量、随机、开放试验,筛选36例合格的健康男性受试者,按1∶1随机分成2组,进食统一高脂餐后,一组服用受试制剂,另一组服用参比制剂,给药剂量均为50 mg。受试者在每一周期给药前1 h内和给药后0.5、1、2、4、8、16、24、32、40、48、56、72、96、120、168、336和504 h进行血样的采集。采用液相色谱串联质谱(HPLC-MS/MS)法测定人血浆中比卡鲁胺的浓度,用SAS 9.4软件非房室模型法分析药代动力学(PK)参数。结果36例入组受试者均完成研究并进行了PK分析。血浆中受试制剂和参比制剂比卡鲁胺的C_(max)、AUC_(0-72h)、AUC_(0-t)及AUC_(0-∞)的几何均值的比值分别为98.20%、99.63%、102.33%和102.18%,对应的90%置信区间分别为91.19%~105.75%,92.34%~107.49%,90.83%~115.28%,88.61%~117.82%。本研究未发生严重不良事件(SAE),无受试者因不良事件(AE)退出研究,试验过程中不良事件发生率为36.1%,均为1级,药物不良反应发生率为11.1%,未采取任何治疗措施。结论比卡鲁胺胶囊与比卡鲁胺片在高脂餐后的中国健康男性受试者中具有生物等效性,且安全性和耐受性良好。Objective To evaluate the bioequivalence and safty of bicalutamide capsules after eating high-fat meal in Chinese healthy volunteers.MethodsSingle-dose,open,randomized,two preparations,parallel study,36 enrolled healthy subjects were randomly divided into two equal groups,one group took the test preparation and the other group took the reference preparation after eating high-fat meal.The dosage was 50 mg.Blood samples were collected within 1 h before administration and 0.5,1,2,4,8,16,24,32,40,48,56,72,96,120,168,336 and 504 h after administration.The plasma concentration of bicalutamide was determined by HPLC-MS/MS and pharmacokinetic(PK)parameters were calculated via SAS 9.4 software.Results All 36subjects completed the study and conducted PK analysis.The ratios of geometric mean values of C_(max),AUC_(0-72h),AUC_(0-t)and AUC_(0-∞)of test preparation and reference preparation in plasma were 98.20%,99.63%,102.33%and 102.18%respectively.The corresponding 90%confidence intervals of the ratios were 91.19%-105.75%,92.34%-107.49%,90.83%-115.28%,88.61%-117.82%.There were no serious adverse events(SAE)in this study,and no subjects withdrew from the study due to adverse events(AE).AE occurred with a incidence of 36.1%were all grade 1,without any treatment.The incidence of adverse drug reactions(ADR)was 11.1%.Conclusion The two preparations are bioequivalent in Chinese healthy subjects after high-fat meal with good safety and tolerability.

关 键 词：比卡鲁胺 高脂餐 生物等效性 药代动力学 前列腺癌 

分 类 号：R979.1[医药卫生—药品]