TABLE 1

Nelfinavir drug-related parameters

Parameter	Unit	Value	Reference
Physicochemical and blood-binding properties
Molecular weight	g/mol	567.80	ChEMBL DrugBank
Log P_o:w		4.07	Longer et al., 1995
Ionization pattern		Diprotic base
pKa		6,11.06
B/P		1.00	Zhang et al., 2001
F_u		0.014	Zhang et al., 2001
Plasma binding component		AAG	Motoya et al., 2006
Absorption phase
Model		ADAM
P_app	10⁻⁶ cm/s, Caco2	7.11	Kim et al., 1998
Solubility	mg/ml	4.50	Longer et al., 1995
Distribution phase
Prediction method		Full PBPK model Method 1
Vss	l/kg	2.00 for healthy5.20 for pregnancy	Predicted by Simcyp
Elimination phase
CL_iv	l/h	37.70	Sarapa et al., 2005
CL_int,CYP3A (f_m,CYP450)	μl/min/pmol CYP450	1.30 (25.19%)
CL_int,CYP2C19 (f_m,CYP450)	μl/min/pmol CYP450	29.62 (15.99%)
CL_int,CYP2C9 (f_m,CYP450)	μl/min/pmol CYP450	0.90 (8.72%)
CL_int,CYP1A2 (f_m,CYP450)	μl/min/pmol CYP450	0.99 (6.30%)
CL_int,CYP2E1 (f_m,CYP450)	μl/min/pmol CYP450	1.43 (11.63%)
CL_int,CYP2D6 (f_m,CYP450)	μl/min/pmol CYP450	8.19 (10.17%)
Additional HLM CL_int (f_m)	μl/min/mg protein	145.24 (12.00%)
CL_int,bile (f_CLbile)	μl/min/million cells	26.35 (10.00%)
CL_R (f_e)	l/h	0.57 (2.00%)
Drug interactions
Inhibition
K_inact,CYP3A	min⁻¹	0.16	Kirby et al., 2011
K_app,CYP3A	μmol/l	1.82	Kirby et al., 2011
K_i,CYP3A	μmol/l	4.80	Lillibridge et al., 1998
K_i,CYP2C19	μmol/l	126.00
K_i,CYP1C19	μmol/l	192.00
Induction
E_max,CYP3A		11.20	Kirby et al., 2011
EC50_CYP3A	μmol/l	6.50	Kirby et al., 2011

ADAM, Advanced Dissolution, Absorption, and Metabolism model; B/P, blood-to-plasma partition ratio; CL_int,bile, intrinsic biliary clearance; CL_int,CYPx, intrinsic clearance via the listed CYP450 isozyme; CL_iv, intravenous clearance; CL_R, renal clearance; EC50_CYP3A, nelfinavir concentration that produces half-maximal induction of CYP3A; E_max,CYP3A, maximal fold induction of CYP3A relative to control; f_CLbile, fraction of drug excreted in the bile; f_e, fraction of drug excreted in the urine; f_m,CYP450, fraction metabolized by CYP450 enzymes; f_u, unbound fractions in plasma; K_app,CYP3A, concentration of mechanism-based inhibitor associated with half-maximal inactivation rate of CYP3A enzymes; k_i,CYPx, concentration of inhibitor that produces half-maximal inhibition of CYP450 isozyme; k_inact,CYP3A, maximum inactivation rate of CYP3A; pKa, acid dissociation constant; P_o:w, octanol-water partition coefficient; Vss, steady-state volume of distribution.