TABLE 2

Physiological and kinetic parameters for modeling in rats and humans

RatHuman
Physiological Parameters
    Weight (g/kg)a
        Liver41.224.1
        Extracellular space in liver11.56.7
        Brain6.85.3
        Lung4.016.7
        Muscle488429
        Kidney9.24.43
    Blood flow ratea (ml/min/kg)
        Liver55.220.7
        Brain5.310.0
        Lung17274.9
        Muscle30.010.7
        Kidney36.915.7
Kinetic parameters
    Plasma unbound fractionb0.640.47
    Liver unbound fraction0.51c0.51d
    Blood/plasma ratioe0.590.56
    Fraction absorbed0.62f0.47g
    Renal clearance (ml/min/kg)1.5h11.3i
    Absorption rate constant (min−1)j0.00880.0078
    Tissue/blood concentration ratio
        Brain0.0360.033k
        Lung0.740.67k
        Muscle0.220.20k
        Kidney1413k

  • ↵a The volume and blood flow rate in each tissue were taken from Davies and Morris (1993) and Kawai et al. (1994). The tissue volume was converted to tissue weight based on the assumption that the tissue gravity is 1 g/ml.

  • ↵b Yamazaki et al. (1996c) and manufacturer's interview form.

  • ↵c Yamazaki et al. (1996b).

  • ↵d Assumed negligible interspecies difference between rat and human.

  • ↵e Yamazaki et al. (1996c) and Lennernäs and Fager (1997).

  • ↵f Komai et al. (1992).

  • ↵g Estimated from the bioavailability (0.18) and hepatic availability (0.38) (Singhvi et al., 1990).

  • ↵h Obtained from the urinary excretion data for intravenous administration of 10 mg/kg.

  • ↵i Singhvi et al. (1990).

  • ↵j Estimated by noncompartment analysis.

  • ↵k Estimated by Kp = fB/fT.