Zidovudine toxicity to murine bone marrow may be affected by the exact frequency of drug administration.
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.
Agur
Z
Z
Department of Applied Mathematics & Computer Science, Weizmann Institute of Science, Rehovot, Israel.
Arnon
R
R
Sandak
B
B
Schechter
B
B
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage / Q000633:toxicity*
D015215:Zidovudine; D004247:DNA