Mechanism of aprindine induced agranulocytosis: direct toxicity on CFU-C and CFU-GEMM.
The in vitro bone marrow growth of 2 patients with aprindine-induced agranulocytosis was studied. Granulocyte-macrophage committed stem cell (CFU-C) growth is inhibited by aprindine in a dose dependent manner. 50% inhibition of CFU-colony growth (TD50) was seen at 5.1 and 3.4 micrograms aprindine/ml medium respectively. The TD50 of control marrow CFU-C was 3.2 micrograms/ml. 100% inhibition was seen at 16 micrograms aprindine/ml, both in patients and controls. Pluripotential stem cell growth (CFU-GEMM) in control marrow was equally inhibited in a dose dependent manner by aprindine, though to a lesser extent (TD50: 9.1 micrograms/ml) and with relative sparing of pure megakaryocyte and erythroid colonies. Co-culturing of patients marrows with their respective acute phase serum did not inhibit CFU-C growth.
D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced*; D000920:Antibody-Dependent Cell Cytotoxicity; D001073:Aprindine / Q000009:adverse effects*; D001854:Bone Marrow Cells; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007192:Indenes / Q000009:adverse effects*; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D013234:Stem Cells
D007192:Indenes; D001073:Aprindine