TABLE 3

Pharmacokinetic properties of basimglurant

Pharmacokinetic properties of basimglurant in male adult rat and male nonhuman primate (mean of n = 2–4 per species and route), as well as mean plasma protein binding and CL_int in liver microsomes and hepatocytes from rat, nonhuman primate, and human (mean of n ≥ 2 per species).

Properties	Rat	Cynomolgus		Human
Properties	Rat	Fasted	Fed	Human
Dose p.o./i.v. (mg/kg)	3/1	0.3/1.0
C_max (ng/ml)	240^{^a}	76.5^{^a}	36.1^{^a}
T_max (h)	2.3^{^a}	1^{^a}	2^{^a}
T_1/2 (h)	7.5^{^a}	∼20^{^a}
CL (ml/min/kg)	6.0^{^b}	9.1^{^b}
V_SS (l/kg)	3.7^{^b}	5.1^{^b}
Oral bioavailability, F (%)	42^{^a}^,^{^b}	∼100%^{^a}^,^{^b}^,^{^c}	54^{^a}^,^{^b}
Brain/plasma ratio	1.7–2.9^{^d}
Protein binding (%)^{^e}	97.9	98.0		98.6
CL_int in microsomes(µl/min per mg protein at 1 µM)^{^f}	10.9	14.1		6.4
CL_int in hepatocytes (µl/min per 10⁶ cells at 1 µM)^{^f}	6.6	0.2		0.3

CL, clearance; CL_int, intrinsic clearance; t_1/2, half-life; T_max, time after administration to peak plasma concentration; V_ss, volume of distribution.
↵^a PK parameters derived after p.o. administration.
↵^b PK parameters derived after i.v. administration.
↵^c Estimated because i.v. and p.o. doses were not identical.
↵^d Brain/plasma ratios obtained in the dose range of pharmacodynamic and pharmacokinetic studies.
↵^e Pooled plasma.
↵^f Pooled from male animals or from male and female human donors.