枸橼酸西地那非片在中国健康受试者体内的生物等效性研究  

Bioequivalence study of sidenafil citrate tablets in Chinese healthy subjects

作　　者：李晓斌[1] 陈璐 吴秀君[1] 葛宇鑫 陆文超 肖婷 谢荷 王华伟[1] 王文萍[1] LI Xiao-bin;CHEN Lu;WU Xiu-jun;GE Yu-xin;LU Wen-chao;XIAO Ting;XIE He;WANG Hua-wei;WANG Wen-ping(Phase Ⅰ Clinical Trial Ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoninng Province,China;China Resources Saike Medical&Pharmaceutical Co.,Ltd.,Beijing 101100,China;Anhui Wanbang Pharmaceuticals Techonology Co.,Ltd.,Hefei 230088,Anhui Province,China)

机构地区：[1]辽宁中医药大学附属医院GCP中心Ⅰ期临床病房,辽宁沈阳110032 [2]华润双鹤药业股份有限公司,北京101100 [3]安徽万邦医药科技股份有限公司,安徽合肥230088

出　　处：《中国临床药理学杂志》2024年第3期430-434,共5页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁省中药临床药物代谢动力学重点实验室基金资助项目;辽宁省教育厅课题资助项目(辽教办[2023]274号)。

摘　　要：目的 评估在空腹、餐后条件下健康受试者口服枸橼酸西地那非片(100 mg)受试制剂与参比制剂的生物等效性。方法 用单次给药、随机、开放、两周期、双交叉设计。空腹和餐后试验各入组36例健康受试者,每周期单次口服枸橼酸西地那非片受试制剂和参比制剂100 mg。用液相色谱-串联质谱法(LC-MS/MS)检测人血浆中西地那非及N-去甲基西地那非的浓度,用Analyst 1.6.3(AB Sciex)以非房室模型计算药代动力学参数,评价2种制剂的生物等效性,并对试验期间受试者进行相关的安全性评价。结果 空腹试验西地那非受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(494.69±230.94)和(558.78±289.83)ng·mL^(-1),AUC_(0-t)分别为(1 336.21±509.78)和(1 410.82±625.99)h·ng·mL^(-1),AUC_(0-∞)分别为(1 366.49±512.16)和(1 441.84±628.04)h·ng·mL^(-1)。餐后试验西地那非受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(381.89±126.53)和(432.47±175.91)ng·mL^(-1),AUC_(0-t)分别为(1 366.34±366.99)和(1 412.76±420.37)h·ng·mL^(-1),AUC_(0-∞)分别为(1 403.28±375.32)和(1 454.13±429.87)h·ng·mL^(-1)。空腹和餐后试验受试制剂和参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比的90%置信区间均在80%~125%内,判断2种制剂具有生物等效性。空腹和餐后试验的不良事件发生率分别为33.33%和25.00%,未发生严重不良事件。结论 枸橼酸西地那非片受试制剂和参比制剂具有生物等效性,安全性良好。Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured (100 mg) test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,twoperiod,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst1.6.3 (AB Scie) using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:C_(max)were (494.69±230.94) and(558.78±289.83) ng·mL^(-1),AUC_(0-t)were (1 336.21±509.78) and (1 410.82±625.99) h·ng·mL^(-1),AUC_(0-∞)were (1 366.49±512.16) and (1 441.84±628.04) h·ng·mL^(-1),respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:C_(max)were (381.89±126.53) and (432.47±175.91)ng·mL^(-1),AUC_(0-t)were (1 366.34±366.99) and (1 412.76±420.37) h·ng·mL^(-1),AUC_(0-∞)were(1 403.28±375.32) and (1 454.13±429.87) h·ng·mL^(-1),respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were33.33%and 25.00%,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

关 键 词：枸橼酸西地那非片 N-去甲基西地那非 生物等效性 安全性 

分 类 号：R97[医药卫生—药品]