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

Table 4

Summary pharmacokinetics observed in three species and predicted in human.

		Rat	Dog	Monkey	Human predicted
IV; 1 mg/kg	Clearance (mL/min/kg)	24.3 ± 1.7	5.7 ± 1.7	15.2 ± 5.9	5.6
	AUClast (nM·h)	1484 ± 121	6640 ± 2257	2632 ± 926
	Half-life (hour)	2.0 ± 0.3	5.2 ± 1.4	4.0 ± 0.5	13
	MRT (hour)	1 ± 0.2	6.6 ± 2.0	3.8 ± 0.7
	Vss (L/kg)	1.8 ± 0.5	2.2 ± 0.8	3.7 ± 1.3	5.2
PO suspension 5 mg/kg	AUClast (nM·h)	3995 ± 964	4546 ± 2157	2031 ± 1038
	𝐶max (nM)	674 ± 227	487 ± 155	219 ± 94
	𝑇max (hour)	3.3 ± 1.2	1.7 ± 0.6	2.0 ± 0
	𝐹 (%)	54%	13%	16%	28%

MRT-mean residence time; AUClast-area under the plasma concentration-time curve from zero time until the last quantifiable concentration.