Kume Y, Maeda F, Harashima H, Kiwada H
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
J Pharm Pharmacol. 1991 Mar;43(3):162-6. doi: 10.1111/j.2042-7158.1991.tb06658.x.
Multilamellar vesicles (300-350 nm) were infused into the rat femoral vein at the rate of 4, 40 and 400 nmol phosphatidycholine min-1 for 6 h using [3H]inulin as an aqueous marker. The time courses of blood concentration of vesicles, normalized for infusion rate, were not superimposable, showing the non-linearity of liposome disposition in the blood circulation. These time courses of blood concentration were well fitted by a single Michaelis-Menten equation. On the other hand, the time courses of tissue content could not be so accommodated. Additionally, the observed relationship between the uptake of liposomes by the liver and their clearance from it and other organs differed essentially from a simulation based on Michaelis-Menten type saturable kinetics. Therefore, it is suggested that there is a time-dependent non-Michaelis-Menten type process in the phagocytosis of macrophages in the reticuloendothelial system.
以[³H]菊粉作为水溶性标记物，将多层囊泡（300 - 350纳米）以4、40和400纳摩尔磷脂酰胆碱每分钟的速率注入大鼠股静脉，持续6小时。经输注速率归一化后的囊泡血药浓度时间进程无法叠加，表明脂质体在血液循环中的处置呈非线性。这些血药浓度时间进程可用单一的米氏方程很好地拟合。另一方面，组织含量的时间进程则不能如此拟合。此外，观察到的肝脏对脂质体的摄取与其从肝脏及其他器官清除之间的关系，与基于米氏型饱和动力学的模拟结果有本质差异。因此，提示网状内皮系统中巨噬细胞的吞噬作用存在时间依赖性的非米氏型过程。
