2095704-43-9

To investigate the pharmacodynamic properties of SLV-2436 (SEL201), 5 consecutive oral doses of 10, 25, and 50 mg/kg are administered to mice every 12 hours (twice-daily schedule). At the 10 mg/kg twice-daily dosage, 4 hours after the fifth administration, a low plasma concentration of 125 ng/mL SLV-2436 is determined. However, dosing at 25 and 50 mg/kg twice daily, equivalent to 50 and 100 mg/kg/d of SLV-2436, yields substantially increased dose-dependent plasma exposure, reaching an average level of 1,299 ng/mL and 2,075 ng/mL, respectively. At the 24-hour time point, SLV-2436 is still detectable in the plasma, with dose-dependent concentrations of 9, 73, and 124 ng/mL in the 10, 25, and 50 mg/kg twice-daily treatment groups. Oral (p.o.) administration of SLV-2436 at the dosage of 50 mg/kg twice daily, that is, 100 mg/kg/d, for 37 days is well tolerated in mice^[1].