Abstrait

Experimental model of reversible myelosuppression caused by shortterm, high-dose oxazolidinone administration

Emily J Hickey, CJ Gill, AS Misura, AF Flattery and GK Abruzzo

Aims: To develop a murine model of oxazolidinone-induced myelosuppression observed in man for identification of potentially less myelosuppressive compounds within this chemical therapeutic class. Methods: Female C3H mice were treated orally, once-daily, with linezolid for between 2 and 7 days. A total of 24 h after the last dose, mice were euthanized, blood was collected by cardiac puncture and analyzed for hematologic parameters against vehicle control animals. Results: Results from three independent experiments demonstrated that oral treatment with linezolid at 50 mg/kg produces mild, reversible anemia characterized by reticulocytopenia in greater than 4 days in mice. Conclusions: Use of this model to screen potential chemotherapeutic agents will facilitate discovery and guide structure–activity relationship chemistry for less myelosuppressive compounds.