ABSTRACT
The pharmacodynamic efficiency of nitroglycerin (TNG) is 3 to 4 times higher than that of isosorbide dinitrate (ISDN). In a previous work the authors have shown that this difference is partially due to the transmembrane diffusion potential of the molecules. The aim of this present study is to confirm this hypothesis by using artificial solid lipid membranes and thus to validate the method which will be used to predict the transmembrane diffusion of drugs. Two types of artificial membranes, having nearly the same liposolvent properties as the biological membrane, are tested to investigate intracellular drug penetration. These artificial membranes are fitted on the Dibbern's three phases apparatus: the Resomat 2. The results are in accordance with the data obtained on erythrocyte membranes showing that both drugs have a good transmembrane diffusibility and also that TNG presents a quicker intracellular penetration than ISDN. These results contribute to validate this method, using artificial membranes, to predict the intracellular penetration of molecules.
Subject(s)
Cell Membrane/metabolism , Isosorbide Dinitrate/pharmacokinetics , Membranes, Artificial , Nitroglycerin/pharmacokinetics , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Humans , In Vitro Techniques , PermeabilityABSTRACT
Nitroglycerin pharmacodynamic efficiency is 3 to 4 times higher than isosorbide dinitrate efficiency. Authors put forward that this difference is at least partially pertained to the transmembrane diffusion potential of the molecules. Data of this first study on red cell membranes are in accordance with this hypothesis.
Subject(s)
Erythrocyte Membrane/metabolism , Isosorbide Dinitrate/metabolism , Nitroglycerin/metabolism , Cell Membrane Permeability , Diffusion , Humans , Time FactorsABSTRACT
Nitroglycerin pharmacodynamic efficiency is 3 to 4 times higher than isosorbide dinitrate efficiency. Data of this study on physiological and artificial membranes point the greater nitroglycerin transmembrane diffusion, which is discussed as a possible relevant explanation.
