Kinetics of Drug Action by J. M. van Rossum (auth.), Prof. Dr. Jacques M. van Rossum

By J. M. van Rossum (auth.), Prof. Dr. Jacques M. van Rossum (eds.)

Most medications, pollution, hormones, and so forth result in their biologic activities through reacting with particular receptors someplace within the physique. Scientists operating in all components of biologic technological know-how have proven expanding curiosity within the research of drug-receptor interactions within the broadest feel. experiences of gear (binding) to receptors in situ and to remoted and in part purified receptors have gotten universal perform. The motion of a drug within the physique is, in spite of the fact that, a kinetic occasion not just with appreciate to move of drug molecules to the surroundings of the receptors, but additionally with admire to the drug-receptor interplay itself. Kinetics of Drug motion is an integrative method of drug delivery during the physique, membrane delivery towards the receptors, and the kinetics of drug­ receptor interplay. This quantity is aimed toward offering a serious and penetrating examine of the issues proper to the kinetics or drug motion from drug dosage to the ultimate reaction. it really is felt that the severe surveys offered during this quantity will give a contribution considerably to receptor examine examine in a variety of biologic fields and to a greater realizing of drug motion. i need to precise my gratitude to our secretary leave out MARGOT JANSSEN for the vast typing of manuscripts and to our laboratory assistant pass over COBY HURKMANS for her committed suggestions within the correcting a number of the manuscripts and preparating the index.

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Physicochemical Fundamentals and Thermodynamics ofthe Membrane Transport of Drugs 17 because of its specific binding to cell components. The investigations of MITCHELL [202,203], KEYNES [152], GLYNN [90], USSING and ZERAHN [304], MAIZELS [191], and KABACK and STADTMAN [135], however, prove that this mode of uphill movement can ultimately be excluded, because the actively transported particles are freely movable in the cytoplasm and osmotically effective. Furthermore, cells emptied of their cell content may nevertheless actively accumulate several permeants.

The phenomenologic treatment of the carrier transport follows that of simple diffusion. As is shown by the kinetics, the accelerated membrane passage of a solute A can be described as diffusion of the permeant-carrier complex AC. Therefore the solute flow JA becomes an AC-specific flux, JAC , the permeability coefficient of which, WAC, is greater than the A-specific quantity WA. If the driving force of JA = JAC is expressed in terms of A concentrations, instead of L1 CA = C~ - c~ in simple diffusion of A [cf.

Therefore transport by carrier mechanism and by diffusion are indistinguishable under these conditions (D kinetics according to WILBRANDT and ROSENBERG [325]). The differentiation between these two transport mechanisms is only possible at higher permeant concentrations. It should be noted at low concentrations of A the transport is inversely proportional to the dissociation constant K AC . (c) For c~, c~ ~ K AC , Equation (82) leads to (85) In this case the transport is directly proportional to K AC and depends further on the difference of the reciprocals of the permeant concentrations.

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