Parameters used for the erythromycin breath test simulations
| Description (units) | Notation | Value | Reference/Comments |
|---|---|---|---|
| Dose (mmol) | 0.074 | ||
| Volume of kidney (liters) | VKD | 0.270 | Freitas (1999) |
| Volume of lung (liters) | VLG | 0.775 | Freitas (1999) |
| Volume of vein (liters) | Vvein | 2.700 | Freitas (1999) |
| Volume of the combined other organs (liters) | VOT | 52.337 | Calculated based on Freitas (1999) |
| Volume of artery (liters) | Vart | 2.700 | Freitas (1999) |
| Volume of extracellular space in the liver (liters) | VES | 0.340 | Calculated based on Freitas, (1999), Levitt (2003), Jamei et al. (2014), |
| Effective volume of extracellular space in the liver (liters) | VES, eff | 0.543 | Based on modification of Eq. 2 of Jamei et al. (2014) |
| Volume of hepatocyte (liters) | VLC | 1.139 | Calculated based on Freitas (1999), Levitt (2003), Jamei et al. (2014) |
| Blood flow of kidney (l/h) | QKD | 66 | Rowland and Tozer (2005) |
| Estimated glomerular filtration rate (l/h) | eGFR | 5.964 | Average value of this cohort of the 12 healthy subjects |
| Total body blood flow (l/h) | QTotal | 300 | Rowland and Tozer (2005) |
| Blood flow of the combined other organs (l/h) | QOT | 136 | Calculated based on Rowland and Tozer (2005) |
| Blood flow of hepatic artery (l/h) | QLV, Art | 98 | Calculated based on Grillo et al. (2012); portal blood hepatic artery blood flow was combined to simplify the model |
| Blood flow of hepatic vein (l/h) | QLV, Vein | 98 | Grillo et al. (2012) |
| Total passive diffusion between extracellular space and hepatocyte (l/h) | QES-LC | 227 | Yabe et al. (2011) |
| Clearance via hepatic uptake transport (l/h) | CLUP1 | 212.29 | Yabe et al. (2011 |
| Clearance via P-gp (l/h) | CLOUT1 | 0.347 | Assumed based on an initial simulation using Frassetto et al. (2007) |
| Clearance via MRP2 (l/h) | CLOUT2 | 1.735 × 10−4 | Calculated by Vmax and Km |
| Clearance via CYP3A4 (l/h) | CLCYP | 176.4 | Kanamitsu et al. (2000) |
| Fraction unbound in blood | fu,BL | 0.27 | Assumed based on Sun et al. (2010) |
| Fraction unbound in extracellular space | fu,ES | 0.425 | Calculated based on Khor and Mayersohn (1991), Araki et al. (2002), Langer et al. (2005), and Paine et al. (2008) |
| Fraction unbound in hepatocyte | fu,LC | 0.05 | Yabe et al. (2011) |
| Partition coefficient of lung to plasma | PLG:P | 0.33 | Assumed based on Gaohua et al. (2015) |
| Partition coefficient of the combined other organs to plasma | POT:P | 0.801 | Calculated based on Björkman (2002), Jansson et al. (2008), Sun et al. (2010) |
| Partition coefficient of blood to plasma | PBL:P | 0.854 | Grillo et al. (2012) |
| Partition coefficient of kidney to plasma | PKD:P | 2.23 | Grillo et al. (2012) |
| Partition coefficient of hepatocyte to plasma | PLC:P | 2.71 | Grillo et al. (2012) |
| Partition coefficient of extracellular space to plasma | PES:P | 1.10 | Assumed based on partition coefficient of epithelial lining fluid to plasma in Gaohua et al. (2015) |
| Maximum velocity of hepatic uptake transport (mmol/h) | Vmax, UP1 | 9.6833 × 10−3 | Freitas (1999), Barter et al. (2007), Yabe et al. (2011), Heikkinen et al. (2016) |
| Michaelis constant of MRP2 (mM) | Km, OUT2 | 64.4 × 10−3 | Franke et al. (2011) |
| Maximum velocity of transport by MRP2 (mmol/h) | Vmax, OUT2 | 11.17314 × 10−6 | Franke et al. (2011) |
| Elimination constant of bicarbonate (h−1) | kresp | 12.72 | Sugiyama et al. (2011) |