Abstract
AZT and ACV are nucleoside analogs which are clinically useful in the treatment of infections caused by the human immunodeficiency virus and by herpes viruses, respectively. Since both agents must enter cells in order to exert their antiviral activity, the mechanism of their cell membrane permeation has been investigated. Unlike most nucleoside-like compounds, AZT was found to permeate human erythrocytes and lymphocytes chiefly by nonfacilitated diffusion and not via the nucleoside transport system (J. Biol. Chem. 262, 5748-5754 (1987)). In subsequent studies it was found that 2′, 3′-dideoxythymidine (ddThd) also entered human erythrocytes chiefly by nonfacilitated diffusion, thus indicating that the unusual cell membrane permeation behavior of AZT is due largely to elimination of the 3′-hydroxyl moiety of thymidine. However, the rate of nonfacilitated diffusion of AZT into these cells was 2- to 3-fold greater than that of ddThd, indicating that the increased lipophilicity conferred on AZT by its 3′-azido moiety enhances its penetration of cell membranes. Although often referred to as an “acyclic nucleoside,” ACV has been found to permeate the human erythrocyte membrane solely via the same purine nucleobase carrier which transports adenine, guanine and hypoxanthine and not via the nucleoside carrier. Elucidation of the unusual transport properties of these two antiviral drugs may contribute to our understanding of their human pharmacokinetics and disposition.
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Zimmerman, T., Prus, K., Mahony, W. et al. 186 3′-AZIDO-3′-DEOXYTHYMIDINE (AZT) AND ACYCLOVIR (ACV): ANTIVIRAL NUCLEOSIDE ANALOGS WITH UNUSUAL CELL MEMBRANE PERMEATION PROPERTIES. Pediatr Res 24, 142 (1988). https://doi.org/10.1203/00006450-198807000-00210
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DOI: https://doi.org/10.1203/00006450-198807000-00210