. 2019 Mar 6;11(3):108. doi: 10.3390/pharmaceutics11030108

Table 2.

Input parameters for PBPK modeling of PA and NAPA.

Parameter	Value (CV%)		Comments
Parameter	PA	NAPA	Comments
Physchem and Blood Binding
Molecular weight	235.33	277.36	-
Compound type	Monoprotic base		-
pKa	9.04	9.04	Predicted ^a
log P	0.83	0.93	Predicted ^a
$f_{u p}$	0.870	0.688	Measured (PA), estimated (NAPA)
B/P ratio ( $R$ )	1	1	Assumed (see text) [28]
Distribution ( $K_{p}$ )
Kidney	8.31	31.2	Corrected with ER ^b
Liver	11.7	19.6	Corrected with ER ^b,c
Brain, heart, lung, and spleen	-	-	Determined (Same with $K_{p, s s}$ ) ^c
Other tissues	-	-	Predicted—Rodgers and Rowland method [49]
Semi-Mechanistic Kidney
$C L_{u, i n t, r}$ (mL/min)	4.67 (16.0)	9.16 (22.5)	Retrograde calculation ^b
$P S_{i n}$ (mL/min)	16.2	20.3	Retrograde calculation ^b
$P S_{o u t}$ (mL/min)	7.61	7.61 ^d	Scaled from PAMPA permeability [44,54] ^e
$C L_{r a b s}$ (mL/min)	0.415	0.415 ^d	Retrograde calculation ^b
$E R$ ^f	0.316	0.327	Determined (see text)
$f_{u, k i d n e y}$	0.223	0.0588	Predicted—Rodgers and Rowland method [49]
Non-Renal Elimination
$C L_{u, i n t}$ (mL/min)	69.0	2.88	Retrograde calculation ^b
$E R$ ^f	0.756	0.0918	Determined (see text)
F_NAPA	0.534		Retrograde calculation ^b

^a ChemAxon MarvinSketch 15.5.11.0 (http://www.chemaxon.com/products/marvin); ^b See text for detailed calculations; ^c For the co-treatment condition, $K_{p}$ values for brain, heart, lung, and spleen tissues were adopted from the $K_{p, s s}$ values experimentally determined in this study. For the liver compartment, extraction ratio estimated from calculated CL_NR of PA and NAPA was used for the correction of $K_{p, s s}$ ; ^d In this study, parallel artificial membrane permeability assay (PAMPA) permeability and reabsorption clearance of NAPA was assumed to be the same with PA; ^e $S_{e f f}$ normalized by g kidney was multiplied by the volume of proximal tubule cells, assuming the tissue density is unity; ^f Extraction ratio determined for the control group.