In vivo pharmacokinetic and absence of toxicity effect of APO866 in mice. (A) Plasma concentration (nM) of APO866 following a single intraperitoneal dose of 20 mg/kg is above the EC50 values of the cell lines used for xenograft studies for at least 8 hours. Three mice were killed at each time point, and a Li-Heparin stabilized blood sample was obtained and analyzed for APO866 concentration using HPLC-MS/MS as described in “Methods.” Error bars represent SD. (B) APO866 treatment did not induced any weight loss in mice. Test SCID mice (n = 10) were treated intraperitoneally with 20 mg/kg APO866, twice daily for 4 days, repeated weekly 3 times. Control mice (n = 10) received vehicle only. Groups of animals were compared with respect to variation of their weight by statistical analysis using the one-way ANOVA. (C) Counts of lymphocytes, neutrophils, and monocytes in tail vein blood samples of mice treated intraperitoneally with 20 mg/kg APO866 twice daily for 4 days. Blood samples were taken before treatment (pre) and on the day after the last treatment with APO866 (post). The P values of paired t tests comparing the pre- and posttreatment lymphocyte, neutrophil, and monocyte counts, respectively, are indicated on the figure. ***P < .001; NS indicates difference not statistically significant.
