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  • Title: The kinetics of drug-membrane interactions in human erythrocytes.
    Author: Eskelinen S.
    Journal: Can J Physiol Pharmacol; 1987 Dec; 65(12):2373-8. PubMed ID: 3449193.
    Abstract:
    The time course of the shape transformations and vesicle release in human erythrocytes caused by lysophosphatidylcholine and chlorpromazine was monitored using a light microscope-video recording technique. The time required for the erythrocytes to reach a stage I echinocytic shape decreased from 4.0 to 2.0 s, when the concentration of the lysophosphatidylcholine solution injected was increased from 1 to 25 microM. The time required to reach stage II decreased from 8.3 to 3.5 s and that required for vesicle release and the formation of stage IV spherocytes decreased from 78.0 to 11.6 s. Correspondingly, the time needed for the formation of stage I stomatocytes decreased from 2.3 to 1.0 s and that for stage II stomatocytes from 3.1 to 2.0 s, when the ambient chlorpromazine concentration was increased from 50 to 200 microM. The kinetics of the shape transformations of the erythrocytes were dependent on the ambient drug concentration. The rate of shape transformations could be predicted from a formula derived for the kinetics of the incorporation of the detergent into the cell membrane, providing that the affinity coefficient and mass transfer coefficient for drugs changed as a function of the free drug concentration. The results give a time scale for the drug-membrane interactions, i.e., the formation of stages I and II for drug-lipid bilayer interactions and the release of vesicles for drug-cytoskeleton interactions.
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