Table 1:
Physiological Parameters
| Parameter | Description | Value | Units | Source |
|---|---|---|---|---|
| Volumes | ||||
| BW | Body Weighta | 70 | kg | [Brown et al., 1997] |
| Vadi | Fraction of body weight as adipose | 21.4 | Unitless | [Brown et al., 1997] |
| Vk | Fraction of body weight as kidney | 0.4 | Unitless | [Brown et al., 1997] |
| Vl | Fraction of body weight as liver | 2.6 | Unitless | [Brown et al., 1997] |
| Vrp | Fraction of body weight as rapidly perfusedb | 9.6 | Unitless | [Brown et al., 1997] |
| Vsp | Fraction of body weight as slowly perfused c | 58.0 | Unitless | [Brown et al., 1997] |
| Vap | Fraction of body weight as arterial blood |
2.0 | Unitless | [Brown et al., 1997] |
| Vvp | Fraction of body weight as venous blood | 6.0 | Unitless | [Brown et al., 1997] |
| Flow Rates | ||||
| Qco | Cardiac output | 312 | L/hr | [Brown et al., 1997] |
| BP | Blood:plasma ratio | 0.55d | Unitless | [Ramakrishnan et al., 2016] |
| Qadi | Fraction cardiac output to adipose | 5.2 | Unitless | [Brown et al., 1997] |
| Qk | Fraction cardiac output to kidney | 17.5 | Unitless | [Brown et al., 1997] |
| Ql | Fraction cardiac output to liver | 22.7 | Unitless | [Brown et al., 1997] |
| Qrp | Fraction cardiac output to rapidly perfused | 25.5 | Unitless | [Brown et al., 1997] |
| Qsp | Fraction cardiac output to slowly perfused | 29.1 | Unitless | [Brown et al., 1997] |
| Qap | Fraction cardiac output to arterial blood | 1.5 | Unitless | [Brown et al., 1997] |
| Qvp | Fraction cardiac output to venous blood | 4.4 | Unitless | [Brown et al.,1997] |
| Partition coefficients | ||||
| D adipose/plasma partition coeffi-cient | 2.4 | Unitless | [Heaney et al., 2009] | |
| D kidney/plasma partition coefficiente | 1.02 | Unitless | [Heaney et al., 2009] | |
| D liver/plasma partition coefficient | 1.02 | Unitless | [Heaney et al., 2009] | |
| D rapidly perfused/plasma partition coefficientf | 0.44 | Unitless | [Heaney et al., 2009] | |
| D slowly perfused/plasma partition coefficient | 0.42 | Unitless | [Heaney et al., 2009] | |
| 25(OH)D adipose/plasma partition coefficient | 0.11 | Unitless | [Heaney et al., 2009] | |
| 25(OH)D kidney/plasma partition coefficient | 0.23 | Unitless | [Heaney et al., 2009] | |
| 25(OH)D liver/plasma partition coefficient | 0.23 | Unitless | [Heaney et al., 2009] | |
| 25(OH)D rapidly perfused/plasma partition coefficient | 0.08 | Unitless | [Heaney et al., 2009] | |
| 25(OH)D slowly perfused/plasma partition coefficient | 0.05 | Unitless | [Heaney et al., 2009] | |
| Kinetic Parameters | ||||
| Michelis-Menten constant for CYP27A1 | 3.2 | μmol/L | [Sakaki et al., 2005] | |
| In vitro maximum velocity for CYP27A1 | 0.269 | mol/min/mol p450 |
[Sakaki et al., 2005] | |
| Michelis-Menten constant for CYP2R1 | 0.45 | μmol/L | [Shinkyo et al., 2004] | |
| In vitro maximum velocity for CYP2R1 | 1.2 | mol/min/mol p450 |
[Shinkyo et al., 2004] | |
| Michelis-Menten constant for CYP27B1 | 0.9 | μmol/L | [Tang et al., 2012] | |
| In vitro maximum velocity for CYP27B1 | 1.3 | nmol/min/mg p450 |
[Tang et al., 2012] | |
| Michelis-Menten constant for CYP24A1 | 0.16 | μmol/L | [Sakaki et al., 2005] | |
| In vitro maximum velocity for CYP24A1 | 0.088 | mol/min/mol p450 |
[Sakaki et al., 2005] | |
| P450liv | Conversion factor for CYP enzymes in liver | 11 | nmol p450/g liver | [Wilson et al., 2003] |
| P450kid | Conversion factor for CYP enzymes in kidney | 12.8 | mg p450/g kidney | [Al-Jahdari et al., 2006] |
| CYP27A1 | Enzyme fraction for CYP27A1 | 0.010 | Unitless | optimized |
| CYP2R1 | Enzyme fraction for CYP2R1 | 0.075 | Unitless | optimized |
| CYP27B1 | Enzyme fraction for CYP27B1 | 0.016 | Unitless | optimized |
| CYP24A1 | Enzyme scalar for CYP24A1 | 0.012 | Unitless | optimized |
| Additional Parameters | ||||
| Kabs | Absorption constantg | 0.88 | hr−1 | estimated |
| UnbD | Unbound percentage of vitamin D | 0.083 | Unitless | optimized |
| Unb25 | Unbound percentage of 25(OH)D | 0.03 | Unitless | [Bikle et al., 1986] |
| h | Hill coefficient | 4.0 | Unitless | optimized |
| Effect level for vitamin Dh | 4.08 | nmol/L | optimized | |
| Effect level for 25(OH)D | 4.45 | nmol/L | optimized | |
D, Vitamin D; 25, 25(OH)D
Reference body weight. Organ density is assumed to be 1 kg = 1 L
Richly perfused tissues included adrenal, blood , brain, gastrointestinal tissues, heart, lungs and thyroid. This compartment served as a mass balance compartment, namely 100 — ∑c VC for other compartments c
Poorly perfused tissues included muscle, skin, and bone
Plasma flow rates assumed a hematocrit value of 0.45 as vitamin D and its metabolites are primarily bound to plasma compounds
Kidney measurements were not taken in Heaney et al. [2009]; this partition coefficient was set equal to the rapidly perfused tissue
Measurements were set to the “remainder” compartment as given in [Heaney et al., 2009]
Estimated using the half-life of vitamin D [Zerwekh, 2008] and the time to maximum concentration [Heaney and Armas, 2015]