KINETIC-STUDIES ON CYTOSINE-ARABINOSIDE PERMEATION THROUGH THE EGG PHOSPHATIDYLCHOLINE LIPOSOMAL MEMBRANE

We analyzed the permeability of low-molecular weight drugs through the lipid bilayer membrane using a new model. This model (model 3) was co mpared with two conventional models (models 1 and 2) in the permeation behavior of cytosine arabinoside (ara-C) through mixed cholesterol-ph osphatidylcholine liposomes using a dialysis bag. In models 1 and 2 th e ara-C permeation rate is calculated based on the following premise: 1) The rate is proportional to the first degree of the difference betw een the equilibrium concentration in the external medium of the dialys is bag at time t=infinity, and the concentration at each time. 2) The rate is proportional to the first degree of the concentration differen ce between the inside and outside of the liposomes. Analysis using mod el 3 was performed on the premise that the ara-C permeation rate is pr oportional to the first degree of the concentration difference between the inside and outside of the liposomes and that between the inside a nd outside of the dialysis bag. The ara-C permeation coefficients thro ugh the liposomal membrane obtained using models 1, 2, and 3 were 2.9 x 10(-5), 1.7 x 10(-6), and 1.7 x 10(-9) (cm/min), respectively. The m odels were evaluated according to Akaike's information criteria (AIC) and the sum of squares (SS). The best results were obtained using mode l 3 (AIC= -29.7, SS=1.2 x 10(-1)). These results suggest that the film resistance inside the dialysis bag should be considered one of the ra te determining steps of drug permeation in an experimental system in w hich the outside but not the inside of the dialysis bag is agitated.