摘要目的 探讨国产达沙替尼在慢性髓性白血病慢性期(CML-CP)患者的药代动力学特征及与原研达沙替尼制剂的生物等效性比较.方法 采用随机、平行、交叉、自身对照设计进行试验.12例对甲磺酸伊马替尼或尼洛替尼耐药或不耐受的CML-CP患者,随机先给予受试制剂(国产达沙替尼,商品名依尼舒)或参比制剂(原研达沙替尼,商品名施达赛)100 mg后,再自身交叉给予同剂量另一种制剂,采用高效液相色谱-串联质谱法测定患者血浆达沙替尼的浓度,估算达沙替尼的药代动力学参数及2种制剂的人体生物等效性.结果 受试制剂与参比制剂的各主要药代动力学参数:药峰浓度(Cmax)分别为(209.01±58.69)μg/L和(223.07士79.51)μg/L;达峰时间(Tmax)分别为(1.1士0.8)h和(1.1±0.8)h;末端清除半衰期(T1/2)分别为(5.10士1.34)h和(4.39±0.74)h;曲线下面积(AUC)0-t分别为(646.65士185.67)h·μg/L和(695.84273.40)h·μg/L;AUC0-∞分别为(668.11士186.00)h·μg/L和(712.424278.08)h·μg/L.平均驻留时间(MRT)分别为(5.32±1.70)h和(4.68士1.53)h.两药间各参数差异均无统计学意义(P值均＞0.05).对主要药动学参数进行等效性检验,两种制剂在CML-CP患者吸收速率和吸收程度均等效,差异无统计学意义(JP值均＞0.05).结论 国产达沙替尼和原研产品应用于CML-CP患者后两种制剂生物等效.

abstractsObjective To evaluate the pharmacokinetics and bioequivalence of genetic dasatinib in patients with chronic myeloid leukemia in the choronie phase(CML-CP).Methods Using randomized,parallel,overlapping,self-control designed study,a 100 mg dose of the reference or test tablet was given to 12 CML-CP patients who were resistant or intolerant to Imatinib and Nilotinib in a randomized two-way crossover design,and the plasma concentration of the medicine was assayed by HPLC-MS-MS.The main pharmacokinetic parameters and bioequivalence of the two formulations were evaluated.Results The major pharmacokinetic parameters were as follows:Cmax (209.01±58.69) μg/L and (223.07±79.51) μg/L,Tmax (1.1±0.8) h and (1.1±0.8) h,T1/2 (5.10±1.34) h and (4.39±0.74) h,AUC0.t (646.65±185.67) h·μg/L and (695.84±273.40) h·μg/L (all P＞0.05);AUC0-x(668.11±186.00) h·μg/L and (712.42±278.08) h·μg/L,MRT (5.32± 1.70) h and (4.68± 1.53) h (all P＞0.05).Conclusion The two formulations were bioequivalent.