Table 1.

Drug-specific input parameters of diazepam.

Parameters	Values		Ref.
Physicochemical Properties
Molecular Weight (g/mol)	284.74		[40]
LogPo:w	2.82		[35]
pKa	3.4		[41]
Absorption
Model
Peff,man (cm/s)	12.434 × 10−4 a,b		[35]
PSA (Ao)	32.67		[39]
HBD	0		[39]
Distribution
Model Prediction Method	The Rodger and Rowland Method + Ion Membrane Permeability
B/P ratio	0.58		[41]
fu	0.03		[3,42]
Vss (L/kg)	0.66 a,c		[35,43]
For Intranasal Administration
Lung fa	0.7 d
Lung ka	1.6 d,e
Elimination
fumic	0.59 a
N-demethylation	Vmax (pmol/min/pmol)	Km (μM)
CYP2B6	3.6	113	[44]
CYP2C19	2.3	32
CYP3A4	14.8	1828
CYP3A5	1.8	293
3-hydroxylation
CYP2B6	0.1	150	[44]
CYP2C19	20.2	846
CYP3A4	151.3	2235
CYP3A5	48.4	316

^a Value predicted by Simcyp, ^b reported value, ^c the reported value range was 0.59−1 L/kg, ^d adjusted by manual optimization, ^e adjusted to 3.2 while simulating supersaturated solution, blood-to-plasma ratio (B:P), fraction unbound (f_u), Michaelis–Menten constant (K_m), maximum rate of metabolic formation (V_max), the volume of distribution at steady-state (V_ss), human jejunum permeability (P_eff), polar surface area (PSA), hydrogen bonding donor (HBD), acid dissociation constant (pKa), octanol–water partition coefficient (LogP_o:w), fraction absorbed (f_a), and absorption rate constant (k_a).