TABLE 1.

Model parameters for clarithromycin

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

^a K_m was estimated in-house using human liver microsomes. V_max was estimated by CL_{int, 3A} × K_m. V_{max, non3A} was estimated as 10% of V_{max, 3A}. V_{max, 3A} was assumed to be equivalent between the gut wall and liver.

^b Calculated from CL_int (Chu et al., 1992) and in vitro K_m (Rodrigues et al., 1997).

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