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Antimicrobial Agents and Chemotherapy, Feb 1997, 460-464, Vol 41, No. 2
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Increased activation of the combination of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of hydroxyurea

S Palmer and S Cox
Virology Department, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden.

The intracellular phosphorylation of 3'-azido-3'-deoxythymidine and 2'- deoxy-3'-thiacytidine was increased two- to threefold by the addition of hydroxyurea (HU) to the single drugs or to the two drugs in combination. The ratios of drug triphosphate to competing cellular deoxynucleoside triphosphate were increased two- to threefold for both 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of HU. These HU-induced increases in 3'-azido-3'-deoxythymidine and 2'- deoxy-3'-thiacytidine metabolism may further enhance the anti-human immunodeficiency virus activity of these two drugs.

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