多西他赛亚微乳注射液在犬体内的药动学

目的研究多西他赛(DTX)亚微乳注射液在比格犬体内的药动学,比较亚微乳注射液与普通注射液犬体内药动学差异。方法采用单剂量双周期自身交叉设计,Beagle犬前肢分别静脉滴注(20 mg.m-2)DTX亚微乳注射液和DTX注射液(泰素帝),分别于0、0.33、0.67、1、1.5、2、2.5、3、4、6、8、12、24 h采血,血浆中DTX采用液相色谱-质谱联用(LC-MS)法测定。结果相同剂量的DTX亚微乳或普通注射液的AUC0-24分别为(476.80±96.18)和(451.94±43.91)μg.h.L-1,Cmax分别为(510.06±168.58)和(466.71±73.14)μg.L-1,t1/2分别为(5.76±4.24)和(4.40±0.51)h,2种制剂的各药动学参数无显著性差异(P>0.05)。结论多西他赛制成亚微乳制剂后,两者具有相似的体内药动学行为。亚微乳制剂DTX的药-时曲线下面积和峰浓度有所增加,消除半衰期延长可能与制剂形式不同有关。

Pharmacokinetics of docetaxel sub-micro emulsion in Beagle dogs

Objective To study the pharmacokinetics of the docetaxel sub-micro emulsion and evaluate the differences between the sub-micro emulsion and docetaxel injection.Methods We compared docetaxel sub-micro emulsion and its injection with the same iv dosage（20 mg·m-2） in Beagle dogs with cross-over protocol.In the pharmacokinetic study,blood samples were collected at 0,0.33,0.67,1,1.5,2,2.5,3,4,6,8,12,and 24 h and its concentration in the plasma was determined by HPLC-MS.Results AUC and Cmax of docetaxel sub-micro emulsion were higher than those of docetaxel injection of the same dosage [（476.79±96.19）vs（451.94±43.91） μg·h·L-1,（510.06±168.58）vs（466.71±73.14） μg·L-1];the half-life of distribution（t1/2β） was（5.76±4.24） and（4.40±0.51） h,respectively.Other pharmacokinetic parameters had no significant differences.Conclusion The pharmacokinetics of docetaxel sub-micro emulsion change obviously.It can raise the AUC and prolong the resident time of drugs in the blood circulation.