Table 3.

Input parameters for PBPK modeling of cimetidine.

Parameter	Value (CV%)	Comments
Physchem and Blood Binding
Molecular weight	252.34	-
Compound type	Monoprotic base	-
pKa	6.9	Measured [58,59]
log P	0.48	Measured [58]
$f_{up}$	0.836	Measured [56]
B/P ratio ($R$)	1	Assumed (see text) [57]
Distribution
$V_C$ (mL)	83.7 (6.78)	Fitted
$V_1$ (mL)	125 (63.4)	Fitted
$V_2$ (mL)	200 (80.0)	Fitted
$C{L}_{D1}$ (mL/min)	17.6 (22.7)	Fitted
$C{L}_{D2}$ (mL/min)	2.96 (138)	Fitted
$K_{p,KI}$	10.3	Corrected with ER using $K_{p,ss}$ measured [60]
Semi-Mechanistic Kidney
$C{L}_{u,int,r}$ (mL/min)	0.140	Retrograde calculation a
$P{S}_{in}$ (mL/min)	839	Retrograde calculation a
$P{S}_{out}$ (mL/min)	74.1	Scaled from PAMPA permeability [44,61]
$ER$	0.102	Determined (see text)
$f_{u,kidney}$	0.918	Predicted – Rodgers and Rowland method [49]
Non-Renal Elimination
CLH (mL/min)	2.79	Calculated (see text)
Transporter Inhibition
$K_{i,rOCT2}$ (μM)	9.4	Measured [62]
$K_{i,rMATE1}$ (μM)	3.01	Assumed (see text) [63]

^a See text for detailed calculations.