Parameter | CLp.o. clinical and CLp.o. Simcyp | CLHIM+HLMSimcyp | Source |
---|---|---|---|
Dose: 60 mg q.d. | Single and multiple dose | Single and multiple dose | |
Log P | 6.86 | 6.86 | ACD prediction |
Blood/plasma ratio | 1 | 1 | Default value |
pKa | Monoprotic base (8.98B, 8.67A1, 9.56A2) | Monoprotic base (8.98B, 8.67A1, 9.56A2) | ACD prediction |
fu, blood | 0.05 | 0.05 | Physicians' Desk Reference, 2005 |
fu, gut | 1 | 0.05a | Estimated |
fa | 0.60 | 0.60 | Physicians' Desk Reference, 2005 |
Ka | 2.0 | 2.0 | Calculated from 1/Tmax (Morello et al., 2003) |
Qgut (l/h) | 7.6 | 7.6 | Predicted from Jeong et al., 2004 |
Vss (l/kg) | 47 | 47 | Physicians' Desk Reference, 2005 |
CLp.o. (l/h) | 3087 | N.A. | Physicians' Desk Reference, 2005 |
HIM UGT | |||
Vmax, pmol · min−1 · mg−1 | 2183.5 | Dalvie et al., 2008 | |
Km, μM [fu, mic] | 5.5 [0.11] | Dalvie et al., 2008 | |
HLM UGT | |||
Vmax, pmol · min−1 · mg−1 | 3.3 | Dalvie et al., 2008 | |
Km, μM [fu, mic] | 11.2 [0.11] | Dalvie et al., 2008 | |
CYP3A4 | |||
Vmax, pmol · min−1 · mg−1 | 539.6 | Dalvie et al., 2008 | |
Km, μM [fu, mic] | 3.8 [0.11] | Dalvie et al., 2008 | |
KI, μM [fu, mic] | 7.96 [0.049] | 7.96 [0.049] | Experimental |
kinact, min−1 | 0.158 | 0.158 | Experimental |
Ki, μM [fu, mic] | 2.2 [0.42] | 2.2 [0.42] | Pearson et al., 2007 |
CLrenal, l/h | 0 | 0 | Hochner-Celnikier, 1999 |
CYP3A5 Ki, μM [fu, mic] | 1.25 [0.0546] | 1.25 [0.0546] | Pearson et al., 2007 |
ACD, Advanced Chemistry Development, Toronto, ON, Canada; B, base; A1, acid 1; A2, acid 2; N.A., not available.
↵a fu, gut value set to fu, p (see Materials and Methods).