尼洛替尼胶囊在中国健康受试者空腹状态下的生物等效性研究

Bioequivalence study of nilotinib capsules in Chinese healthy volunteers under fasting conditions

目的研究健康成年受试者空腹状态下单次口服受试制剂尼洛替尼胶囊与参比制剂尼洛替尼胶囊(达希纳®)的生物等效性。方法采用单剂量、随机、开放、两制剂、两周期、交叉对照的试验设计,空腹条件入组64例受试者;试验随机分为两组(T-R组和R-T组),单次口服受试制剂(T)0.2 g和参比制剂(R)200 mg,用液相色谱-串联质谱(LC-MS/MS)法测定血浆中尼洛替尼的浓度,应用WinNonlin®8.2软件计算药代动力学参数,应用SAS 9.4软件评价生物等效性。结果受试者空腹服用受试制剂或参比制剂后,尼洛替尼药代动力学参数如下:C_(max)分别为(507.67±155.96)、(457.95±176.30)ng/ml;AUC_(0-t)分别为(10293.63±3634.11)、(9810.67±3929.39)ng·h/ml;AUC_(0-∞)分别为(10900.19±4237.58),(10814.34±4871.26)ng·h/ml。受试制剂和参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)经对数转换后90%可信区间分别为107.62%~122.18%、101.62%~113.68%、98.24%~111.02%。结论两种尼洛替尼胶囊在中国健康受试者体内具有生物等效性。

Objective To study the bioequivalence of the single oral test nilotinib capsules and reference nilotinib capsules(Tasigna®)in Chinese healthy adult volunteers under fasting conditions.Methods This was a single-dose,randomized,open-label,double-sequence,twoperiod,crossover designed study.A total of 64 volunteers were enrolled under fasting condition.Volunteers were randomly divided into two groups(T-R and R-T),single oral test formulation 0.2 g and reference formulation 200 mg.The plasma concentrations of nilotinib were determined by a LC-MS/MS method.The pharmacokinetic parameters were calculated with WinNonlin®8.2 and the bioequivalence was evaluated through SAS 9.4 software.Results After the volunteers administrated test and reference formulations under fasting conditions,the pharmacokinetic parameters of nilotinib as follows:C_(max) of(507.67±155.96)and(457.95±176.30)ng/ml,AUC_(0-t) of(10293.63±3634.11)and(9810.67±3929.39)ng·h/ml,AUC_(0-∞)of(10900.19±4237.58)and(10814.34±4871.26)ng·h/ml,respectively.The 90%confidential interval of the log-transformed C_(max),AUC_(0-t) and AUC_(0-∞)for the test and reference formulation under fasting conditions were 107.62%~122.18%,101.62%~113.68%,98.24%~111.02%,respectively.Conclusion Two kinds of nilotinib capsules were bioequivalent in Chinese healthy volunteers.