Model parameters for clarithromycin

Midazolam PK parameters
    kGL (h−1)1.2 ± 0.52Chien et al., 2006
    V1 (liters)43 ± 8.6Chien et al., 2006
    V2 (liters)88.4 ± 17.7Chien et al., 2006
    fu0.04Chien et al., 2006
    CLper (l/h)59.5Chien et al., 2006
    CLR (l/h)0.06Chien et al., 2006
    CLint, 3A (l/h)439Chien et al., 2006
    CLint, non3A (l/h)36Chien et al., 2006
    Vmax, 3A(mg/h)2600a
    Vmax, non3A (mg/h)250a
    Km (μM)5.8Chien et al., 2006
Clarithromycin PK parameters
    kGL (h−1)1.7 ± 0.73Chu et al., 1992
    V1 (liters)123 ± 24.6
    CLR (l/h)7.5Chu et al., 1992
    CLint (l/h)67Chu et al., 1992
    Vmax, 3A (mg/h)4002 ± 800.4b
    Km (μM)60Rodrigues et al., 1997
    fu0.28Ito et al., 2003
Physiological parameters
    VGW (liters)0.25Chien et al., 2006
    VPV (liters)0.07Ito et al., 2003
    VH (liters)2.8Ito et al., 2003
CYP3A enzyme parameters
    kdeg (h−1)0.025c
    Ki, clar (μM)300Obach et al., 2006
  • a Km was estimated in-house using human liver microsomes. Vmax was estimated by CLint, 3A × Km. Vmax, non3A was estimated as 10% of Vmax, 3A. Vmax, 3A was assumed to be equivalent between the gut wall and liver.

  • b Calculated from CLint (Chu et al., 1992) and in vitro Km (Rodrigues et al., 1997).

  • c kdeg was estimated from in vivo data on CYP3A recovery following clarithromycin (Gorski et al., 2002; Wang et al., 2004).