奥拉帕利片在中国成年肿瘤患者中的生物等效性研究  

Bioequivalence study of olaparib tablets in Chinese adult cancer patients

作　　者：孙成[1] 胡海勋 王孟锦 张燕[1] 姜彬 吕郭金 周宇 SUN Cheng;HU Hai-xun;WANG Meng-jin;ZHANG Yan;JIANG Bin;LÜGuo-jin;ZHOU Yu(Phase I Clinical Trial Laboratory,Zibo Wanjie Cancer Hospital,Zibo 255213,Shandong Province,China;Qilu Pharmaceutical Co.,Ltd.,Ji’nan 250000,Shandong Province,China;Shanghai Xihua Scientific Co.,Ltd.,Shanghai 201210,China)

机构地区：[1]淄博万杰肿瘤医院Ⅰ期临床试验研究室,山东淄博255213 [2]齐鲁制药有限公司,山东济南250000 [3]上海熙华检测技术服务股份有限公司,上海201210

出　　处：《中国临床药理学杂志》2023年第7期1023-1027,共5页The Chinese Journal of Clinical Pharmacology

基　　金：齐鲁制药(海南)有限公司委托研发课题。

摘　　要：目的 评价奥拉帕利片受试制剂与参比制剂在中国成年肿瘤患者中的生物等效性。方法 用多中心、随机、开放、两制剂、两周期、两序列、交叉、多剂量的稳态生物等效性试验设计。48例中国肿瘤患者被随机分为2组,在餐后状态下,交叉口服奥拉帕利片受试制剂或参比制剂,每次300 mg,每天2次,每个周期连续给药7 d,共2个周期,2个周期间不需要清洗期。用液相色谱-串联质谱法测定人血浆中奥拉帕利的浓度,用SAS V9.4软件计算主要药代动力学参数。结果 连续口服奥拉帕利受试制剂与参比制剂300 mg后的主要药代动力学参数:C_(max, ss)分别为(6 523.00±2 126.00)和(7 345.00±1 956.00)ng·mL^(-1),AUC_(0-τ)分别为(4.18±1.68)10^(4)和(4.23±1.49)10^(4)ng·mL^(-1)·h,t_(max, ss)分别为3.00和3.00 h。2种制剂的C_(max, ss)和AUC_(0-τ)经对数转换后的几何均值比的90%置信区间分别为82.21%~90.20%和91.33%~99.44%。结论 2种奥拉帕利片在中国成年肿瘤患者中具有生物等效性。Objective To evaluate the bioequivalence of olaparib tablets between test formulation and reference formulation in Chinese adult cancer patients.Methods A multi-center,randomized,open-label,two-preparations,two-period,two-sequence,crossover,multi-dose,steady-state bioequivalence test was designed.Forty eight Chinese cancer patients were randomly divided into two groups.Under the postprandial state,the test(T)or the reference(R)preparations of olaparib tablets were taken orally in a cross way,300 mg each time,twice a day,for 7 consecutive days in each cycle,a total of 2 cycles,and no washing period was needed during the 2 weeks.The plasma concentration of olaparib in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS).The main pharmacokinetic parameters were calculated by SAS V9.4 software.Results The main pharmacokinetic parameters after continuous oral administration of 300 mg of olapari test preparation and reference preparation were as follows:C_(max, ss) were(6523.00±2126.00)and(7345.00±1956.00)ng·mL^(-1);AUC_(0-τ)were(4.18±1.68)10^(4) and(4.23±1.49)10^(4) ng·h·mL^(-1);t_(max, ss) were 3.00 and 3.00 h.After logarithmic transformation,the 90%confidence intervals of the geometric mean ratio of C_(max, ss) and AUC_(0-τ)of the two preparations were 82. 21% - 90. 20% and 91. 33% - 99. 44%, respectively. Conclusion Two kinds of olaparib tablets arebioequivalent in Chinese adult cancer patients.

关 键 词：奥拉帕利片 生物等效性 药代动力学参数 

分 类 号：R979[医药卫生—药品]