Assessing drug distribution in tissues expressing P-glycoprotein through physiologically based pharmacokinetic modeling: model structure and parameters determination

Table 1 Input physiological parameters used in PBPK model for IV injection of domperidone to a 30 g body weight mouse.

		Tissue Composition (% of wet tissue weight)[20]			Physiological Data
Tissues	Intra Cellular Water	Extra Cellular Water	Neutral Lipids	Phospholipids	Blood Flow Rate (% of Q_c)^a	Volume (% of BW)	Unbound Fraction to Tissue^b	Partition Coefficient^c (Ptp)
Adipose ^d	0.017	0.1350	0.853	0.002	0.07	0.0700	0.0079	1.7258
Bone + ROB*	0.346	0.1000	0.220	0.0005	0.218	0.0799	0.0327	2.0582
Brain	0.620	0.1620	0.031	0.05	0.031	0.0165	0.0463	2.5722
Gut	0.475	0.2820	0.032	0.015	0.141	0.0253	0.0166	6.2541
Heart	0.456	0.3200	0.017	0.014	0.066	0.0038	0.0212	4.8909
Kidney	0.483	0.2730	0.0148	0.0341	0.110	0.0135	0.0104	10.019
Liver	0.573	0.1610	0.0138	0.0303	0.161	0.042	0.0120	9.2366
Lung	0.446	0.3360	0.0218	0.0162	0.005	0.0073	0.0125	8.2560
Muscle	0.630	0.0790	0.0167	0.0273	0.159	0.384	0.0290	3.9387
Skin	0.291	0.3820	0.0239^d	0.0180^d	0.058	0.1653	0.0156	5.1585
Spleen	0.579	0.2070	0.012	0.0107	0.002^c	0.0035	0.0184	6.3008
Plasma	---	---	0.096	0.0032	---	---	---	---
Arterial blood	---	---	---	---	---	0.0272^d	---	---
Venous blood	---	---	---	---	---	0.0544^d	---	---

^aThe mouse cardiac output value was estimated from the following allometric equation: Qc = 0.235 × BW^0.75; ^b Calculated from equation 7.
^c Calculated from equation 1 using the method of Rodgers and Rowland[20]^d Rat value[23]; * ROB: rest of body

ISSN: 1742-4682