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 CLint in liver microsomes and hepatocytes from rat, nonhuman primate, and human (mean of n ≥ 2 per species).

Dose p.o./i.v. (mg/kg)3/10.3/1.0
Cmax (ng/ml)240a76.5a36.1a
Tmax (h)2.3a1a2a
T1/2 (h)7.5a∼20a
CL (ml/min/kg)6.0b9.1b
VSS (l/kg)3.7b5.1b
Oral bioavailability, F (%)42a,b∼100%a,b,c54a,b
Brain/plasma ratio1.7–2.9d
Protein binding (%)e97.998.098.6
CLint in microsomes(µl/min per mg protein at 1 µM)f10.914.16.4
CLint in hepatocytes (µl/min per 106 cells at 1 µM)f6.60.20.3
  • CL, clearance; CLint, intrinsic clearance; t1/2, half-life; Tmax, time after administration to peak plasma concentration; Vss, 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.