Kinetic Studies on Cytosine Arabinoside Permeation through the Egg Phosphatidylcholine Liposomal Membrane

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We analyzed the permeability of low-molecular weight drugs through the lipid bilayer membrane using a new model. This model (model 3) was compared with two conventional models (models 1 and 2) in the permeation behavior of cytosine arabinoside (ara-C) through mixed cholesterol-phosphatidylcholine liposomes using a dialysis bag.In models 1 and 2 the ara-C permeation rate is calculated based on the following premise : 1) The rate is proportional to the first degree of the difference between the equilibrium concentration in the external medium of the dialysis bag at time t=∞ and the concentration at each time.2) The rate is proportional to the first degree of the concentration difference between the inside and outside of the liposomes.Analysis using model 3 was performed on the premise that the ara-C permeation rate is proportional to the first degree of the concentration difference between the inside and outside of the liposomes and that between the inside and outside of the dialysis bag.The ara-C permeation coefficients through the liposomal membrane obtained using models 1,2,and 3 were 2.9×10^<-5>, 1.7×10^<-6>, and 1.7×10^<-9> (cm/min), respectively. The models were evaluated according to Akaike's information criteria (AIC) and the sum of squares (SS). The best results were obtained using model 3 (AIC=-29.7,SS=1.2×10^<-1>). These results suggest that the film resistance inside the dialysis bag should be considered one of the rate determining steps of drug permeation in an experimental system in which the outside but not the inside of the dialysis bag is agitated.
公益社団法人日本薬学会の論文
1996-05-15

Kinetic Studies on Cytosine Arabinoside Permeation through the Egg Phosphatidylcholine Liposomal Membrane

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