Parameter | Midazolam | 1′-OH Midazolam | 4-OH Midazolam | Source |
---|---|---|---|---|
Molecular weight (g/mol) | 326 | 342 | 342 | ACD |
logP | 2.95 | 2.50 | 2.68 | (Poulin and Theil, 2002); ACD |
Compound type | Base | Ampholyte | Ampholyte | (Andersin, 1991); |
pKa | 6.04 | 13.6; 3.63 | 12.7; 5.53 | ACD |
B/P | 0.6 | 1 (Assumed) | 1 (Assumed) | (Heizmann et al., 1983; Gorski et al., 1998) |
fu,p | 0.03 | 0.15 | 0.13 | Measured |
Absorption | ||||
Model | 1st order | NA | NA | |
Fraction absorbed | 1 | NA | NA | (Smith et al., 1981) |
ka (h−1) | 9.6 | NA | NA | (Smith et al., 1981) |
fu,gut | 1 | NA | NA | Assumed |
Caco-2 permeability (10−6 cm/s) | 32.4 | NA | NA | (Gertz et al., 2010) |
Distribution | ||||
Model | Minimal PBPK | Minimal PBPK | Minimal PBPK | |
Vss (l/kg) | 0.8 | 1.8 (Method 1) | 2.2 (Method 1) | (Heizmann et al., 1983) ; Predicted using Method 1 |
Elimination | ||||
Enzyme kinetics | Table 2 | Table 2 | Table 2 | Measured |
Renal clearance | 0 | 0 | 0 |
ACD, values calculated using Advanced Chemistry Development (ACD/Laboratories) Software V12.5.