TABLE 5

Mouse and rat pharmacokinetics for abemaciclib using a 30 mg/kg oral dose

Data are mean values from three animals.

Parameter	Mouse	Rat
Plasma AUC_{0–24 h} (ng·h/ml)	69,300	52,300
Plasma AUC_{0–24 h} (nM·h)	136,686	103,156
Unbound plasma AUC_{0–24 h} (nM·h)^{^a}	7381	3817
Plasma T_max (h)^{^b}	4	3.3
Plasma C_max (ng/ml)	8470	1500
Plasma C_max (nM)	16,706	2958
Unbound plasma C_max (nM)^{^a}	902	109
Brain AUC_{0–24 h} (ng·h/ml)	13,200	47,900
Brain AUC_{0–24 h} (nM·h)	26,035	94,447
Unbound brain AUC_{0–24 h} (nM·h)	206	406
Brain T_max (h)	2	4
Brain C_max (ng/ml)	1840	1500
Brain C_max (nM)	3629	2958
Unbound brain C_max (nM)^{^a}	29	13
Clearance (ml/min per kg)^{^b}	41	14
Half-life (h)^{^b}	13	6
V_d,ss (l/kg)^{^b}	34	6.0
Oral bioavailability (%)^{^b}	62	43

↵^a Measured f_u values from Table 3.
↵^b Determined from 1 mg/kg (mouse) or 0.5 mg/kg (rat) i.v. and 3 mg/kg (mouse) or 1.0 mg/kg (rat) p.o. doses.