苹果酸舒尼替尼胶囊在中国健康受试者中的生物等效性研究

Bioequivalence study of sunitinib malate capsules in Chinese healthy subjects

目的评估在空腹、餐后条件下健康受试者口服苹果酸舒尼替尼胶囊受试制剂与参比制剂的生物等效性。方法本试验采用随机、开放、单剂量、两周期、两序列、交叉的试验设计。空腹和餐后组各纳入24例健康受试者,分别在空腹或餐后状态下单剂量口服苹果酸舒尼替尼胶囊受试制剂或参比制剂50 mg。用液相色谱-串联质谱(LC-MS/MS)对血浆中舒尼替尼的浓度进行测定。用Phoenix WinNolin 6.4和SAS 9.4软件进行药代动力学参数的计算和生物等效性的评价。结果空腹组受试者口服受试制剂和参比制剂后主要药代动力学参数:C_(max)分别为(34.58±8.12)和(33.41±6.41)ng·mL^(-1),t_(max)分别为7.00(4.00,10.00)和6.00(5.00,10.00)h,AUC_(0-72 h)分别为(1166.99±296.63)和(1128.93±280.52)ng·h·mL^(-1),t_(1/2)分别为(32.68±7.74)和(30.53±7.27)h。餐后组受试者口服受试制剂和参比制剂主要药代动力学参数:C_(max)分别为(32.80±6.62)和(32.22±5.58)ng·mL^(-1),t_(max)分别为9.00(5.00,14.00)和9.00(6.00,16.00)h,AUC_(0-72 h)分别为(1224.92±234.26)和(1241.83±248.72)ng·h·mL^(-1),t_(1/2)分别为(31.55±6.28)和(31.78±5.38)h。在空腹和餐后状态下,两制剂的C_(max)和AUC_(0-72 h)经对数转换后几何均值比值的90%置信区间均在80.00%~125.00%的等效区间内。结论苹果酸舒尼替尼胶囊受试制剂和参比制剂在空腹和餐后状态下均具有生物等效性。

Objective To evaluate the bioequivalence of oral sunitinib malate capsule test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods This trial adopts a randomized,open-ended,single-dose,two-cycle,two-sequence,and crossover trial design.Twenty-four healthy subjects were included in each of the fasting and fed groups.A single-dose oral sunitinib malate capsule test preparation or reference preparation of 50 mg was administered in a fasting or fed state,respectively.The concentration of sunitinib in plasma was determined by validated liquid chromatography-tandem mass spectrometry(LC-MS/MS).The calculation of pharmacokinetic parameters and the evaluation of bioequivalence were performed using Phoenix WinNolin 6.4 and SAS 9.4 software.Results After oral administration of the test preparation and the reference preparation in the fasting group,the main pharmacokinetic parameters:C_(max)were(34.58±8.12)and(33.41±6.41)ng·mL^(-1),t_(max)were 7.00(4.00,10.00)and 6.00(5.00,10.00)h,AUC_(0-72h) were(1166.99±296.63)and(1128.93±280.52)ng·h·mL^(-1),t_(1/2) were(32.68±7.74)and(30.53±7.27)h,respectively.After oral administration of the test preparation and the reference preparation in the fed group,the main pharmacokinetic parameters:the C_(max) were(32.80±6.62)and(32.22±5.58)ng·mL^(-1),t_(max) were 9.00(5.00,14.00)and 9.00(6.00,16.00)h,AUC_(0-72h) were(1224.92±234.26)and(1241.83±248.72)ng·h·mL^(-1),t_(1/2) were(31.55±6.28)and(31.78±5.38)h,respectively.In the fasting and fed states,the 90%confidence intervals of the geometric mean ratio of C_(max) and AUC_(0-72h) after logarithmic conversion of the two preparations were within the equivalent interval of 80.00%-125.00%.Conclusion The test and reference formulations of sunitinib malate capsules exhibit bioequivalence in both fasting and fed states.