TABLE 1.
Parameter | Value | Reference |
---|---|---|
Midazolam PK parameters | ||
kGL (h−1) | 1.2 ± 0.52 | Chien et al., 2006 |
V1 (liters) | 43 ± 8.6 | Chien et al., 2006 |
V2 (liters) | 88.4 ± 17.7 | Chien et al., 2006 |
fu | 0.04 | Chien et al., 2006 |
CLper (l/h) | 59.5 | Chien et al., 2006 |
CLR (l/h) | 0.06 | Chien et al., 2006 |
CLint, 3A (l/h) | 439 | Chien et al., 2006 |
CLint, non3A (l/h) | 36 | Chien et al., 2006 |
Vmax, 3A(mg/h) | 2600a | |
Vmax, non3A (mg/h) | 250a | |
Km (μM) | 5.8 | Chien et al., 2006 |
Clarithromycin PK parameters | ||
kGL (h−1) | 1.7 ± 0.73 | Chu et al., 1992 |
V1 (liters) | 123 ± 24.6 | |
CLR (l/h) | 7.5 | Chu et al., 1992 |
CLint (l/h) | 67 | Chu et al., 1992 |
Vmax, 3A (mg/h) | 4002 ± 800.4b | |
Km (μM) | 60 | Rodrigues et al., 1997 |
fu | 0.28 | Ito et al., 2003 |
Physiological parameters | ||
VGW (liters) | 0.25 | Chien et al., 2006 |
VPV (liters) | 0.07 | Ito et al., 2003 |
VH (liters) | 2.8 | Ito et al., 2003 |
CYP3A enzyme parameters | ||
kdeg (h−1) | 0.025c | |
Ki, clar (μM) | 300 | Obach et al., 2006 |
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.
Calculated from CLint (Chu et al., 1992) and in vitro Km (Rodrigues et al., 1997).
kdeg was estimated from in vivo data on CYP3A recovery following clarithromycin (Gorski et al., 2002; Wang et al., 2004).