Comparative in vitro @entity137 of XXXX and @entity632 in human granulocyte-macrophage progenitor cells.

@entity632 @entity137 @entity5 @entity2664 @entity44727 @entity1398 @entity1370
@entity2664 ( @entity44727 ) has recently been introduced into @entity5 therapy as a possible substitute for the structurally related drug, @entity632 (ADR), because it causes less @entity1370 and fewer gastrointestinal side effects. However, the dose-limiting @entity137 of @entity44727 is pronounced @entity1398 . The in vitro hematoxicity of both drugs in granulocyte-macrophage precursor cells (GM-CFCs) was analyzed using drug-exposure schedules analogous to the principles of the in vivo pharmacokinetics of @entity44727 . Bone-marrow and peripheral-blood cells were exposed to 0.075-20 ng/ml @entity44727 or ADR for 5, 20, 60, and 120 min, and for 14 days. The 14-day exposure resulted in Do values of 0.95 and 0.68 ng/ml for bone-marrow and peripheral-blood GM-CFCs subjected to @entity44727 . Exposure to ADR resulted in Do values of 5.43 and 5.13 ng/ml, respectively. As was the case after 14-day exposure to @entity44727 or ADR, short-term exposure again revealed that peripheral-blood GM-CFCs were more sensitive to both drugs. Moreover, at low concentrations, ADR was less toxic than @entity44727 in both types of GM-CFCs, but was more toxic than @entity44727 when a concentration of 20 ng/ml was used. The intracellular concentration of @entity44727 , as measured by high-performance liquid chromatography, was constantly below 1 ng per 2 X 10(7) cells, even when it was applied at a concentration of 20 ng/ml for an exposure time of 2 h. The fact that such low concentrations of @entity44727 are toxic for hemopoietic precursor cells may explain the myelotoxicity of this drug. However, the difference between the precursor-cell @entity137 of @entity44727 and that of ADR was small when their respective therapeutic doses were taken into consideration. Further analyses of their @entity137 in stem cells and/or the microenvironment would appear to be needed.
