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Cellular Transport of Drugs
Thomas H. Steinberg
Clinical Infectious Diseases
Vol. 19, No. 5 (Nov., 1994), pp. 916-921
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/4458157
Page Count: 6
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The ability of drugs to enter cells and to reach an adequate concentration within the appropriate intracellular compartment may be an important determinant of the efficacy of therapy for infections due to intracellular pathogens. Antibiotics vary considerably in their ability to accumulate within cells. All solutes can be taken up by endocytosis, and some compounds reach high intracellular concentrations after crossing the plasma membrane by diffusion or by specific transport processes. Cellular organelles have properties that affect the intracellular distribution of drugs and that may account for the net accumulation of drugs within cells. An important example is the ability of acidic organelles to trap lysosomotropic weak bases. Cells also express transport proteins that may limit the intracellular accumulation of drugs by secreting them across the plasma membrane into the extracellular medium. Thus, cellular organic anion transporters can decrease the intracellular accumulation of certain antibiotics, and the multidrug-resistance transporter, or p-glycoprotein, confers resistance to antineoplastic agents. Inhibition of organic anion transport may have therapeutic value. A better appreciation of the mechanisms by which drugs accumulate within cells and within specific intracellular compartments may lead to the design of agents that reach higher concentrations at clinically relevant intracellular sites.
Clinical Infectious Diseases © 1994 Oxford University Press