PBPK model variables

Tissue VolumeSymbolMouseHumanReference
Kidney% Body weight1.70.4Brown et al. (1997)
Heart0.50.5Brown et al. (1997)
Eye0.034 (g)15 (g)Mou—Experimental; Hum—Brittanica
Skin16.53.7Brown et al. (1997)
Gut4.21.4Brown et al. (1997)
Liver5.52.57Brown et al. (1997)
Blood4.97.9Brown et al. (1997)
Slowly perfused56.175.7Brown et al. (1997)
Rapidly perfused10.47.5Brown et al. (1997)
Tissue blood flow
Kidney% Cardiac output9.117.5Brown et al. (1997)
Heart6.64.0Brown et al. (1997)
Eye0.05660.00164Mou—Zhi et al. (2012); Hum—Choi et al. (2012)
Skin5.85.8Brown et al. (1997)
Gut14.118.1Brown et al. (1997)
Liver2.04.6Brown et al. (1997)
Slowly perfused34.228.5Brown et al. (1997)
Rapidly perfused28.121.5Brown et al. (1997)
Tissue partioninga
KidneyPK5050Wei et al. (1995)
HeartPH4444Wei et al. (1995)
EyePE3333Wei et al. (1995)
SkinPS2626Wei et al. (1995)
GutPG3535McChesney et al. (1967)
LiverPL193193Wei et al. (1995)
BloodPB7.27.2Tett et al. (1988)
Slowly perfusedPSP1010McChesney et al. (1967); Wei et al. (1995)
Rapidly perfusedPRP150150Wei et al. (1995)
Metabolism affinityKmL (μM)357Optimized from mouse PK
Metabolism max rateVmaxL (μM/h)1171Optimized from mouse PK
Metabolism rate constantMet (h−1)0.154Optimized from human liver microsomes
Plasma protein binding% bound0.450.45Browning (2014)
Glomerular filtration rateGFR0.1250.11Mou—Qi and Breyer (2009)
Secretion affinityKmsec (μM)10001000Optimization
Secretion max rateVmaxsec (μM/h)32,50032,500Optimization
Intestinal absorption
Absorption rateKA (h−1)0.5Tett et al. (1989)
Absorption fractionFA0.75Tett et al. (1989)
Melanin bindingd
Melanin affinityKmmel (μM)217Schroeder and Gerber (2014)
Binding ratioHCQmel0.178Schroeder and Gerber (2014)
Eye melanin concentrationCEME (μM)2.4E04Durairaj et al. (2012)
Skin melanin concentrationCSME (μM)300Browning (2014)
  • a Most partition coefficients were optimized from McChesney et al. (1967), Wei et al. (1995), and Tett et al. (1998). Slowly perfused was an average value of adipose from McChesney et al. (1967) and Wei et al. (1995).

  • b Values for mouse were calculated from liver PK data; human rate constant was calculated from human liver microsomes and optimized to meet the ratio of metabolism vs. clearance reported by Tett et al. (1988, 1989).

  • c Total renal clearance was a function of plasma protein binding and GFR, with secretion coefficients optimized to meet total renal clearance values in tandem with metabolism reported by Tett et al. (1988, 1989).

  • d Melanin binding parameters were taken from a bunch of sources and optimized for human. Skin melanin is for an average person of light colored skin. The value increases up to 4 times based on skin color.