Physiologic volumes, blood flows, and pharmacokinetic parameters used for continued, PD modeling and simulation of mice data [see Ramakrishnan et al. (2016) for details]
Value
Assigned volumes (ml)
Total plasma volume (VP)
0.962
Kidney volume (VK)
0.417
Liver volume (VL)
1.37
Intestine volume (VI)
0.632
Enterocyte volume (Ven) = [fQ ⋅ VI]
0.066
Serosal volume (Vser) = [(1−fQ) ⋅ VI]
0.566
Brain volume (VBr)
0.412
Peripheral compartment volume (Vperi)
18.5
Assigned plasma flows (ml·min−1)
Plasma flow to liver (QL)
1.3
Hepatic arterial plasma flow rate (QHA)
0.26
Plasma flow to intestine (QI)
1.04
Plasma flow to enterocyte (Qen) = (fQ⋅QI)
0.109
Plasma flow to serosa (Qser) = [(1-fQ)⋅QI]
0.931
Plasma flow to kidney (QK)
0.733
Plasma flow to brain (QBr)
0.266
Cardiac output (QCO)
8.04
Assigned parameters [values from Ramakrishnan et al. (2016)]
Fraction of QI to enterocyte region (fQ)
0.105
Fraction of CO to peripheral compartment (fd)
0.0048
Absorption rate constant ka (h-1)
1.61
Intestine degradation rate constant in lumen kdeg (h-1)
0.0012
Net synthesis rate of endogenous 1,25(OH)2D3 [Rsyn (fmol·h−1)]
21.5
Turnover rate constants
Renal Cyp27b1 ()
0.245
Hill coefficient for indirect response of renal Cyp27b1 function (γ2)
2.71
Metabolic intrinsic clearance of 1,25(OH)2D3 via Cyp24a1 (ml·h−1)
Hepatic )
0.001
Intestinal
0.0014
Renal
0.0280
Brain
0.0003
Hill coefficient for indirect response function
Hepatic Cyp24a1 (
1.75
Renal Cyp24a1 ()
3.59
Intestinal Cyp24a1 ()
2.09
Brain Cyp24a1 ()
0.576
Turnover rate constants for Cyp24a1
Liver
0.047
Renal
0.287
Intestinal
0.047
Brain
1.87
Assigned partition coefficients (tissue to plasma concentration ratio) and baseline tissue concentrations (pmol·kg-1)
Kidney (KK)
0.34
Liver (KL)
0.15
Brain (KBr)
0.05
Intestine (intestine, serosa, enterocyte) (KI = Kser = Ken)