Increased activation of the combination of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of hydroxyurea.
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.
Palmer
S
S
Virology Department, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden.
Cox
S
S
D019380:Anti-HIV Agents / Q000378:metabolism*; D002460:Cell Line; D003845:Deoxycytosine Nucleotides / Q000032:analysis; D004357:Drug Synergism; D006918:Hydroxyurea / Q000494:pharmacology*; D019259:Lamivudine / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D013942:Thymine Nucleotides / Q000032:analysis; D015215:Zidovudine / Q000378:metabolism*
D019380:Anti-HIV Agents; D003845:Deoxycytosine Nucleotides; D013942:Thymine Nucleotides; C024107:2'-deoxycytidine 5'-triphosphate; D019259:Lamivudine; D015215:Zidovudine; C024157:thymidine 5'-triphosphate; D006918:Hydroxyurea