Low-dose, sublingual AZT-monophosphate therapy for HIV plus patients?

AZT concentrations as low as 0.001 mg/l inhibit viral replication, while co ncentrations above 0.3 mg/l cause considerable damage to erythroid, myeloid progenitor cells and inhibit blastogenesis in mononuclear cells. Furthermo re, AZT must be converted first to monophosphate and then to diphosphate an d finally to triphosphate by the same enzyme: thymidine kinase (TK). Theref ore, large doses of AZT overwhelm TK, causing massive production of monopho sphate and reducing the production of di and triphosphate. Yet the recommen ded dosage of 100 mg ATT every 4 hours results in a peak concentration of 0 .5 mg/l and a trough concentration of 0.1 mg/l (harmful to human cells and resulting in reduced production of triphosphate). On the other hand, sublin gual administration of 1 mg ATT monophosphate every 8 hours (since the intr acellular half life of AZT triphosphate is 3 hours) would be desirable, res ulting in more damage to the virus and less harm to the patient. Finally, t he small dose of monophosphate ensures that most of the AZT be converted to triphosphate, greatly increasing the efficiency and reducing the likelihoo d of the virus developing resistance due to reverse transcriptase binding t o the similar but non inhibiting mono and diphosphate. (C) 2001 Harcourt Pu blishers Ltd.