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- W2002556854 abstract "We measured the intracellular activation and cytotoxicity of 3′-azido-3′-deoxythymidine (zidovudine, ZDV) and 2′,3′-dideoxyinosine (ddI) when combined at three different clinically relevant combinations of 1:1,1:10, and 10:1 (ZDV:ddI). The activation of ddI to ddA-TP was increased in all three combinations with ZDV, compared to ddI alone. A maximum twofold increase in ddA-TP was observed, which could not be further increased by raising the concentration of ZDV in the combination. On the other hand, the concentration of ZDV in the combination could be reduced to one-tenth while retaining increased activation of ddI. We also examined the cytotoxicity of these combinations in CEM cells, phytohemagglutinin (PHA)-stimulated and resting human peripheral blood mononuclear cells (PBMCs). CEM cells were the least sensitive overall to the drugs. ZDV showed greater cytotoxicity in stimulated PBMCs than resting PBMCs, whereas the reverse was true for ddI. This could be explained by the different activation pathways of these two drugs. The 1:1 and 10:1 ZDV:ddI combinations showed reduced toxicity compared to the separate drugs. These results indicate that ZDV and ddI need not necessarily be combined together at a ratio of ZDV:ddI of 1:1, but that some alteration in the dosages of ZDV or ddI in patients could be possible without loss of the benefits of combined ZDV:ddI therapy." @default.
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- W2002556854 date "1995-10-01" @default.
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- W2002556854 title "Intracellular Activation and Cytotoxicity of Three Different Combinations of 3′-Azido-3′-deoxythymidine and 2′,3′-Dideoxyinosine" @default.
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- W2002556854 doi "https://doi.org/10.1089/aid.1995.11.1227" @default.
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