Microcalorimetry for the Uptake of Ionic Drugs by Erythrocyte Cells and Ghosts. In Relation to a Mechanism of the Drug-induced Hemolysis.:In Relation to a Mechanism of the Drug-induced Hemolysis

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Ionic drugs of chlorpromazine (CPZ), promethazine (PMZ), flufenamic acid (FA) and mefenamic acid (MA) were compared with each other as regards the hemolytic action, the thermodynamics of drug binding to human erythrocyte membrane and the uptake into the cell. (1) All the drugs binding interaction with human erythrocyte was spontaneous and exothermic as indicated by negative signs of free energy and enthalpy changes, and conversely the endothermic heat effect was found to be due to hemolysis and disruption of the membrane structure. (2) Cationic drugs, CPZ and PMZ, were bound and/or inserted to the inner erythrocyte membrane with a high affinity. The reactions were characterized by small negative enthalpy and large positive entropy changes which were contributed by hydrophobic interaction between drugs and the phospholipids in the membrane. While, the human erythrocyte had two kinds of binding sites on the cell membrane for anionic drugs, FA and MA; one strong binding site and other weak site with the lower affinity which were due to both ionic and hydrophobic interactions. About 15% of the bound drugs was penetrated into the intracellular membrane. The first class of the binding site was already saturated before hemolysis and the second class might play a significant role in hemolysis by the drugs. (3) As the results, a tentative mechanism for the ionic drug-induced hemolysis is proposed.
日本熱測定学会の論文