Zidovudine toxicity to murine bone marrow may be affected by the exact frequency of drug administration

Abstract

Zidovudine (azidothymidine, AZT) toxicity to the bone marrow (BM) is a major hindrance to its widespread clinical application in the treatment of the acquired immunodeficiency syndrome (AIDS). In this work we verify the prediction of a mathematical model that cytotoxicity to the host can be reduced when the frequency of drug administration is an integer multiple of the target cell average cycle time (ca. 7 h in murine BM cells). We report in vivo experiments in mice showing that a 7-h frequency of AZT administration is significantly less toxic than other frequencies when peripheral blood parameters and the proportion of BM cells arrested at the S-phase gate of the DNA content distribution are considered.