Identification and Preclinical Pharmacology of the -Secretase Modulator BMS-869780

Table 3

Relationship between dose, plasma AUC, and A𝛽 ABEC.

Dose	Plasma AUC^0--24hr	Brain A𝛽 ABEC^24 hr
	(𝜇M·h)	A𝛽1-42 (%)	A𝛽1-40 (%)
Mouse 30 mg/kg PO solution (observed 0–24 hours)	45.9	30.9	n.d.
Mouse 100 mg/kg PO solution (observed 0–24 hours)	102	55.1	n.d.
Rat 10 mg/kg PO solution (observed 0–24 hours)	46.3	47.0	46.1
Rat 3 mg/kg PO solution (predicted steady state after 3 daily doses)*	18.6	26.9
Human 700 mg PO suspension (predicted steady state)*	17.8	25

∗Dose predicted to achieve A𝛽42 ABEC of ca. 25%.