Lv Wenli, Guo Jianxin, Ping Qineng, Song Yunmei, Li Jin
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Int J Pharm. 2008 Jul 9;359(1-2):118-22. doi: 10.1016/j.ijpharm.2008.03.047. Epub 2008 Apr 11.
To compare pharmacokinetics of intravenous breviscapine liposomes in Beagle dogs, rabbits and rats.
Six Beagle dogs, 6 rabbits and 12 rats were intravenously administrated with breviscapine liposomes and commercial injection (breviscapine solution) by the crossover design (two periods), respectively. Plasma concentration of scutellarin, the main active component in breviscapine, at different time intervals was determined by reverse phase-HPLC. The pharmacokinetic parameters including area under the curve (AUC), clearance (CL(s)) and volume of distribution (V(c)) were calculated.
The plasma concentration-time profiles were fitted to a two-compartment model. Breviscapine liposomes exhibited significant difference from injection in CL((s)) and AUC, examined by a one-way analysis of variance (ANOVA). With regard to both breviscapine liposomes and commercial injection (free breviscapine), the logarithm values of AUC, CL(s) and V(c) were all related to the logarithm of the body weight by the allometric equation: Y=axW(b).
The allometric equation might be applied to extroplate dosage for human from animal data and also for dosage adjustment of breviscapine liposomes in order to achieve same AUC as commercial injection. Compared with the breviscapine solution, breviscapine liposomes delivered more scutellarin into the plasma.
比较灯盏花素脂质体在比格犬、家兔和大鼠体内的药代动力学。
分别采用交叉设计（两个周期），对6只比格犬、6只家兔和12只大鼠静脉注射灯盏花素脂质体和市售注射液（灯盏花素溶液）。采用反相高效液相色谱法测定灯盏花素中主要活性成分灯盏乙素在不同时间间隔的血浆浓度。计算药代动力学参数，包括曲线下面积（AUC）、清除率（CL(s)）和分布容积（V(c)）。
血浆浓度-时间曲线符合二室模型。通过单因素方差分析（ANOVA），灯盏花素脂质体在CL((s))和AUC方面与注射液有显著差异。对于灯盏花素脂质体和市售注射液（游离灯盏花素），AUC、CL(s)和V(c)的对数值均通过异速生长方程Y = axW(b)与体重的对数相关。
异速生长方程可用于根据动物数据外推人体剂量，也可用于灯盏花素脂质体的剂量调整，以达到与市售注射液相同的AUC。与灯盏花素溶液相比，灯盏花素脂质体向血浆中递送的灯盏乙素更多。
