TABLE 1

Parameters used for the erythromycin breath test simulations

Description (units)NotationValueReference/Comments
Dose (mmol)0.074
Volume of kidney (liters)VKD0.270Freitas (1999)
Volume of lung (liters)VLG0.775Freitas (1999)
Volume of vein (liters)Vvein2.700Freitas (1999)
Volume of the combined other organs (liters)VOT52.337Calculated based on Freitas (1999)
Volume of artery (liters)Vart2.700Freitas (1999)
Volume of extracellular space in the liver (liters)VES0.340Calculated based on Freitas, (1999), Levitt (2003), Jamei et al. (2014),
Effective volume of extracellular space in the liver (liters)VES, eff0.543Based on modification of Eq. 2 of Jamei et al. (2014)
Volume of hepatocyte (liters)VLC1.139Calculated based on Freitas (1999), Levitt (2003), Jamei et al. (2014)
Blood flow of kidney (l/h)QKD66Rowland and Tozer (2005)
Estimated glomerular filtration rate (l/h)eGFR5.964Average value of this cohort of the 12 healthy subjects
Total body blood flow (l/h)QTotal300Rowland and Tozer (2005)
Blood flow of the combined other organs (l/h)QOT136Calculated based on Rowland and Tozer (2005)
Blood flow of hepatic artery (l/h)QLV, Art98Calculated 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, Vein98Grillo et al. (2012)
Total passive diffusion between extracellular space and hepatocyte (l/h)QES-LC227Yabe et al. (2011)
Clearance via hepatic uptake transport (l/h)CLUP1212.29Yabe et al. (2011
Clearance via P-gp (l/h)CLOUT10.347Assumed based on an initial simulation using Frassetto et al. (2007)
Clearance via MRP2 (l/h)CLOUT21.735 × 10−4Calculated by Vmax and Km
Clearance via CYP3A4 (l/h)CLCYP176.4Kanamitsu et al. (2000)
Fraction unbound in bloodfu,BL0.27Assumed based on Sun et al. (2010)
Fraction unbound in extracellular spacefu,ES0.425Calculated based on Khor and Mayersohn (1991), Araki et al. (2002), Langer et al. (2005), and Paine et al. (2008)
Fraction unbound in hepatocytefu,LC0.05Yabe et al. (2011)
Partition coefficient of lung to plasmaPLG:P0.33Assumed based on Gaohua et al. (2015)
Partition coefficient of the combined other organs to plasmaPOT:P0.801Calculated based on Björkman (2002), Jansson et al. (2008), Sun et al. (2010)
Partition coefficient of blood to plasmaPBL:P0.854Grillo et al. (2012)
Partition coefficient of kidney to plasmaPKD:P2.23Grillo et al. (2012)
Partition coefficient of hepatocyte to plasmaPLC:P2.71Grillo et al. (2012)
Partition coefficient of extracellular space to plasmaPES:P1.10Assumed based on partition coefficient of epithelial lining fluid to plasma in Gaohua et al. (2015)
Maximum velocity of hepatic uptake transport (mmol/h)Vmax, UP19.6833 × 10−3Freitas (1999), Barter et al. (2007), Yabe et al. (2011), Heikkinen et al. (2016)
Michaelis constant of MRP2 (mM)Km, OUT264.4 × 10−3Franke et al. (2011)
Maximum velocity of transport by MRP2 (mmol/h)Vmax, OUT211.17314 × 10−6Franke et al. (2011)
Elimination constant of bicarbonate (h−1)kresp12.72Sugiyama et al. (2011)