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
林莉莉 1蒋燕 1章钦 1秦慧玲 1张茜 1许杨 2梁伟 3孟林英 3储昭兴 3胡伟1
作者信息
- 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
- 折叠
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:Cmax分别为(2.14±0.27)和(2.27±0.33)μg·mL1,AUC0～72h分别为(105.70±11.20)和(107.72±11.77)pg·mL-1·h,tmax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:Cmax分别为(1.83±0.17)和(1.75±0.22)μg·mL-1,AUC0～72h分别为(102.66±9.18)和(101.57±13.01)μg·mL-1·h,tmax分别为 4.01 和4.99 h.空腹及餐后组参比/受试制剂的Cmax、AUC0～72 h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.
Abstract
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:Cmax were(2.14±0.27)and(2.27±0.33)μg·mL-1,AUC0-72h were(105.70±11.20)and(107.72±11.77)μg·mL-1·h,tmax was 1.49 and 0.99 h;the main pharmacokinetic parameters of teriflunomide in the fed group were as follows:Cmaxwere(1.83±0.17)and(1.75±0.22)μg·mL-1,AUC0-72h were(102.66±9.18)and(101.57±13.01)μg·mL-1·h,tmax was 4.01 and 4.99 h.The 90％confidence intervals for the geometric means of Cmax and AUC0-72h 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Key words
teriflunomide tablet/pharmacokinetics/bioequivalence/food effect引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
维普
万方数据