5'-Nucleotides as potential formulations for administering nucleoside analogs in man.

The kidneys of mice and other small mammals contain relatively high phosphomonoesterase levels. When 5′-nucleotides of 9-β-d-arabinofuranosyladenine and 9-(β-d-arabinofuranosyl)-6-mercaptopurine were administered to mice, they were rapidly dephosphorylated and excreted in the same form and at the same rate as if the nucleosides were given. However, human kidney samples had much lower phosphomonoesterase levels, and when 5′-nucleotides of the 2 nucleoside analogs were administered to patients they were relatively slowly converted to nucleosides and provided sustained blood plasma levels of the nucleosides. This appears to have potential advantages both for providing sustained dosage and for a better dosage formulation, the latter because of the greater solubility of the nucleotides.