特立氟胺片在健康中国受试者体内的药代动力学及生物等效性研究  

Pharmacokinetics and bioequivalence study of teriflunomide tablets in healthy Chinese subjects

作　　者：林莉莉 蒋燕 章钦 秦慧玲 张茜[1] 许杨 梁伟 孟林英 储昭兴 胡伟[1] LIN Li-li;JIANG Yan;ZHANG Qin;QIN Hui-ling;ZHANG Qian;XU Yang;LIANG Wei;MENG Lin-ying;CHU Zhao-xing;HU Wei(Department of Clinical Pharmacology,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601,Anhui Province,China;Anhui Wanbang Pharmaceutical Technology Co.,Ltd.,Hefei 230601,Anhui Province,China;Hefei Enright Pharmaceutical Co.,Ltd.,Hefei 230601,Anhui Province,China)

机构地区：[1]安徽医科大学第二附属医院药物临床试验研究中心,安徽合肥230601 [2]安徽万邦医药科技股份有限公司,安徽合肥230601 [3]合肥恩瑞特药业有限公司,安徽合肥230601

出　　处：《中国临床药理学杂志》2024年第3期425-429,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 比较2种特立氟胺片在中国健康男性体内空腹及餐后条件下的药代动力学相似性,并评价其安全性及生物等效性。方法 用随机、开放、单剂量、平行的试验设计。空腹和餐后分别纳入31例和32例中国健康男性受试者,随机单次服用参比/受试制剂特立氟胺片14 mg。用液相色谱-串联质谱法检测血浆中特立氟胺浓度,用Phoenix WinNonlin 8.1计算主要药代动力学参数,并进行生物等效性分析。结果 在空腹条件下,服用参比/受试制剂特立氟胺后的主要药代动力学参数:C_(max)分别为(2.14±0.27)和(2.27±0.33)μg·mL^(-1),AUC_(0~72h)分别为(105.70±11.20)和(107.72±11.77)μg·mL^(-1)·h,t_(max)分别为1.49和0.99 h。在餐后条件下,服用参比/受试制剂特立氟胺后的主要药代动力学参数:C_(max)分别为(1.83±0.17)和(1.75±0.22)μg·mL^(-1),AUC_(0~72h)分别为(102.66±9.18)和(101.57±13.01)μg·mL^(-1)·h,t_(max)分别为4.01和4.99 h。空腹及餐后组参比/受试制剂的C_(max)、AUC_(0~72h)几何均值90%置信区间都在80%~125%内。结论 2种特立氟胺片在空腹和餐后给药条件下药代动力学特征相似,生物等效,安全性良好;饮食推迟药物的达峰时间。Objective To compare the pharmacokinetic profiles of the two teriflunomide tablets in healthy Chinese subjects under fasting and fed conditions and to evaluate their bioequivalence and safety.Methods A randomized,open,single-dose,parallel trial design was used to enroll 31 and 32 healthy Chinese male subjects in the fasting and fed groups,who were randomized to a single oral dose of 14 mg of either reference or test preparation of teriflunomide tablets.The plasma concentrations of teriflunomide were determined using liquid chromatography-tandem mass spectrometry method,and Phoenix WinNonlin 8.1 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of teriflunomide.The main pharmacokinetic parameters of teriflunomide in the fasting group were as follows:C_(max) were(2.14±0.27) and(2.27±0.33)μg·mL^(-1),AUC_(0-72h) were(105.70±11.20) and(107.72±11.77)μg·mL^(-1)·h,t_(max) was 1.49 and 0.99 h;the main pharmacokinetic parameters of teriflunomide in the fed group were as follows:C_(max )were(1.83±0.17) and (1.75 ± 0.22) μg · m L^(-1),AUC_(0-72h) were(102.66 ± 9.18) and (101.57 ± 13.01) μg · m L^(-1)·h,t_(max) was 4.01 and 4.99 h.The 90% confidence intervals for the geometric means of C_(max) and AUC_(0-72h) for reference and test preparations in the fasting and fed groups were in the range of 80% to 125%.Conclusion The pharmacokinetic characteristics of the 2 formulations were similar under fasting and fed administration conditions,with good bioequivalence and safety;Postprandial administration may delay the time to peak of the drug.

关 键 词：特立氟胺片 生物等效性 药代动力学 安全性 食物影响 

分 类 号：R979.5[医药卫生—药品]