Toxicity of HPA-23 (ammonium-21-tungsto-9-antimoniate) for normal human myeloid progenitor cells (GM-CFU) in vitro.
HPA-23 is a competitive inhibitor of the RNA-dependent DNA polymerase (reverse transcriptase) of the human immunodeficiency virus (HIV). It may therefore potentially benefit patients with HIV infection. This study aimed at defining the haematopoietic toxicity of this drug and particularly its effects on the normal human granulocyte-macrophage progenitor cells (GM-CFU). Our in vitro studies, in semi-solid agar, have shown an inhibitory effect of increasing concentrations of HPA-23 on colony and cluster formation. This effect is probably dose-dependent. An almost complete inhibition of colony formation was observed at doses of more than 20 micrograms/ml. Regarding cluster formation, a similar although much more progressive inhibitory effect was found. Our experimental data should be extrapolated with caution to clinical situations. However, they must be kept in mind for optimal design of HPA-23 therapy in HIV infected patients.
Aymard
J P
JP
Regional Blood Transfusion and Haematology Centre, Nancy, France.
Ferry
R
R
Janot
C
C
Schooneman
F
F
Legras
B
B
May
T
T
Streiff
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000965:Antimony / Q000627:therapeutic use / Q000633:toxicity*; D000998:Antiviral Agents / Q000627:therapeutic use / Q000633:toxicity*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006098:Granulocytes; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014414:Tungsten / Q000627:therapeutic use / Q000633:toxicity*; D017973:Tungsten Compounds
D000998:Antiviral Agents; D017973:Tungsten Compounds; C009613:ammonium tungsten antimonate hydroxide oxide; D000965:Antimony; D014414:Tungsten