Table 1.

Summary of physiological and anatomical variables used for PBPK calculations of PA, NAPA and cimetidine in rats.

Whole-Body PBPK Model a
Tissue	Tissue Volume (mL)	Blood Flow (mL/min)
Adipose	16.7	4.72
Bone	15.7	8.08
Brain	1.24	1.12
Gut	6.19	8.08
Heart	1.05	3.2
Liver	8.57	19.4
Lung	1.24	80
Muscle	116	19
Skin	39.4	4.08
Spleen	0.57	0.88
Venous blood	10.2	-
Arterial blood	5.11	-
Semi-Mechanistic Kidney b
Parameter	Definition	Value
$V_{GLM}$ (mL)	Volume of glomerulus	0.08 [43]
$V_{PTC}$ (mL)	Volume of proximal tubule cells	1.03 [43]
$V_{RBL}$ (mL)	Volume of renal blood	0.375 [43]
$Q_{KI}$ (mL/min)	Blood flow to kidneys	11.6 [42,44]
$GFR$ (mL/min)	Glomerular filtration rate	1.31 [9]
$V_{S1\_1}$ (mL), $Q_{S1\_1}$ (mL/min)	Volume and flow of filtrate in the lumen of 1st sub-segment of S1 segment of proximal tubule	GFR
$V_{S1\_2}$ (mL), $Q_{S1\_2}$ (mL/min)	Volume and flow of filtrate in the lumen of 2nd sub-segment of S1 segment of proximal tubule	0.85 GFR [45,46,47]
$V_{S1\_3}$ (mL), $Q_{S1\_3}$ (mL/min)	Volume and flow of filtrate in the lumen of 3rd sub-segment of S1 segment of proximal tubule	0.70 GFR [45,46,47]
$V_{S2+S3}$ (mL), $Q_{S2+S3}$ (mL/min)	Volume and flow of filtrate in the lumen of S2 and S3 segments of proximal tubule	0.55 GFR [45,46,47]
$V_{LOH}$ (mL), $Q_{LOH}$ (mL/min)	Volume and flow of filtrate in the lumen of Loop of Henle	0.33 GFR [45,46,47]
$V_{DT+CD}$ (mL), $Q_{DT+CD}$ (mL/min)	Volume and flow of filtrate in the lumen of distal tubules and collecting ducts	0.18 GFR [45,46,47]
$V_U$ (mL), $Q_U$ (mL/min)	Volume and flow of urine	0.02 GFR [45,46,47]

^a Parameters (tissue volume and blood flow to tissues) were obtained from the literature [41], which are also used in the Simcyp Software [42] Version 15 Release 1 (Simcyp Limited, Sheffield, UK). ^b Semi-mechanistic kidney model [32,33] was incorporated with minor modifications.