Myelotoxicity of rifabutin and 3'-azido-3'-deoxythymidine, alone and in combination, to human hematopoietic progenitor cells in vitro.
Mycobacterial infection is a common complication of acquired immunodeficiency syndrome (AIDS) frequently requiring antimycobacterial medication. It was of interest to determine if one such agent, rifabutin, could be tolerated by AIDS patients in conjunction with 3'-azido-3'-deoxythymidine (AZT) therapy. We evaluated the in vitro myelotoxic effects of rifabutin on human hematopoietic progenitor cells, alone and in combination with AZT (rifabutin: AZT, 1:10 ratio) over a range of concentrations in a microcapillary assay. Both rifabutin and AZT at 5 microM were moderately toxic to hematopoietic progenitors, inhibiting colony formation by 57-65% and 59-63%, respectively. The combination of rifabutin (5 microM) and AZT (50 microM) inhibited colony formation by 59-73%. Granulocyte-macrophage progenitors were less sensitive to this combination than erythroid progenitors. The combination of ribabutin and AZT did not exceed the in vitro myelotoxicity to human progenitors of AZT alone. These results suggest that rifabutin may be tolerated in AIDS patients, with no anticipated increase in myelotoxicity when given with AZT.
Volpe
D A
DA
Hipple Cancer Research Center, Dayton, OH 45439-2092.
Du
D L
DL
Verhoef
V
V
Murphy
M J
MJ
D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D017828:Rifabutin / Q000633:toxicity*; D015215:Zidovudine / Q000633:toxicity*
D017828:Rifabutin; D015215:Zidovudine