TABLE 4

Murine pharmacokinetic parameters

ParameteraValue for compound:
211121314
i.v.b
    Dose (mg/kg)3015303030
    Cmax (μg/ml) at 5 min8.918.013.713.617.1
    CL (ml/h/kg)2,1803281,119582687
    Vss (ml/kg)2,1169683,8053,1423,221
    MRT (h)2.13.03.45.44.7
    AUC0–∞ (h · μg/ml)13.845.826.851.643.7
    α-t1/2 (h) (% AUC)0.06 (5)0.09 (2)0.11 (7)0.10 (2)0.05 (5)
    β-t1/2 (h) (% AUC)1.5 (95)2.08 (98)2.53 (93)3.83 (98)3.40 (95)
p.o.c
    Dose (mg/kg)3030303030
    Cmax (μg/ml)3.47.25.06.46.3
    Tmax (h)0.501.001.000.250.50
    AUC0–24 (h · μg/ml)13.235.923.847.557.6
    Terminal t1/2 (h)1.82.72.73.13.6
    Bioavailability (%)96398992100
    Mouse PPB (%)6501623
  • a CL, clearance; Vss, volume of distribution at steady state; MRT, mean residence time; t1/2, half-life; Tmax, time to maximum concentration of drug in serum. PPB, plasma protein binding.

  • b WinNonlin two-compartment analysis with iterative weighting.

  • c WinNonlin noncompartmental analysis with uniform weighting.