TABLE 3

Summary tissue–to–serum concentration ratio after dosing in mice (C57BL/6J, male, day 10)

Tissue
Tissue-to-serum ratio (k)
3.85 ± 0.66
Brain
8.59 ± 3.71
TissueQD dose (mg/kg)SampleTime (h)Concentration ± SD (ng/ml or ng/g)Pseudo T1/2(h)
Serum10Cmax1.97258 ± 58.96.33
Cmin25.120.5 ± 9.25
Brain10Cmax1.971010 ± 3849.44
Cmin25.1186 ± 37.5
  • Data are means ± SE, unless otherwise indicated. Serum and brain concentrations of Rimonabant were determined following intraperitoneal dosing once daily for 10 days at 10 mg/kg. On the final day, mice were injected with compound and killed at ∼2 h and ∼25 h postdose and serum and brain collected and processed. The concentrations in the brain are 4–10 times higher than those in the serum at the corresponding time. The ratios at the 25-h collection times are almost two times higher than those observed at the 2-h collection. This suggests an equilibrium delay between the brain and the serum and is the likely source of the longer apparent half-life in the brain versus the serum. The pseudo T1/2 values were determined from the 2- and 25-h time points and are an approximation of the compound's half-life.