Relationship between Hemolytic Concentrations and Physicochemical Properties of Basic Drugs, and Major Factors Inducing Hemolysis

概要

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To clarify the differences in hemolytic activities between basic drugs and to identify the major factors inducing hemolysis, some tranquilizers and antihistaminics were compared with each other as regards hemolytic activities, van der Waals volume (V), pK_a, partition coefficient (octanol/water, P), lipid spin labeling and membrane/buffer partition ratio (P_<m/b>), and correlation analyses were carried out among these parameters. The best correlation was between logarithmic P_<m/b> for drugs and 1/C_1 (C_1 ; the initial concentration inducing hemolysis, r=0.877,p<0.01) or 1/C_<50> (C_<50> ; the concentration inducing 50% hemolysis, r=0.924,p<0.01). Less good correlations were observed between the logarithmic V (r=0.708,p<0.05 ; r=0.780,p<0.05) or the fluidity of lipids (r=0.711,p<0.05 ; r=0.619) and 1/C_1 or 1/C_<50>, respectively. No correlation, however, was found between P and hemolytic concentrations. These results indicate that the amount of drugs penetrated into the membrane is probably a major factor in the induction of hemolysis, and that large molecular volume of a drug, increased fluidity of the membrane lipids and un-ionized concentration of the drug significantly affect the drug-induced hemolytic process.
社団法人日本薬学会の論文
1983-12-25