In nlmixrdevelopment/RxODE.doc: Facilities for Simulating from ODE-Based Models
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How RxODE assigns compartment numbers
RxODE automatically assigns compartment numbers when parsing. For
example, with the Mavoglurant PBPK model the following model may be
used:
library(RxODE)
pbpk <- RxODE({
KbBR = exp(lKbBR)
KbMU = exp(lKbMU)
KbAD = exp(lKbAD)
CLint= exp(lCLint + eta.LClint)
KbBO = exp(lKbBO)
KbRB = exp(lKbRB)
## Regional blood flows
CO = (187.00*WT^0.81)*60/1000; # Cardiac output (L/h) from White et al (1968)
QHT = 4.0 *CO/100;
QBR = 12.0*CO/100;
QMU = 17.0*CO/100;
QAD = 5.0 *CO/100;
QSK = 5.0 *CO/100;
QSP = 3.0 *CO/100;
QPA = 1.0 *CO/100;
QLI = 25.5*CO/100;
QST = 1.0 *CO/100;
QGU = 14.0*CO/100;
QHA = QLI - (QSP + QPA + QST + QGU); # Hepatic artery blood flow
QBO = 5.0 *CO/100;
QKI = 19.0*CO/100;
QRB = CO - (QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI);
QLU = QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI + QRB;
## Organs' volumes = organs' weights / organs' density
VLU = (0.76 *WT/100)/1.051;
VHT = (0.47 *WT/100)/1.030;
VBR = (2.00 *WT/100)/1.036;
VMU = (40.00*WT/100)/1.041;
VAD = (21.42*WT/100)/0.916;
VSK = (3.71 *WT/100)/1.116;
VSP = (0.26 *WT/100)/1.054;
VPA = (0.14 *WT/100)/1.045;
VLI = (2.57 *WT/100)/1.040;
VST = (0.21 *WT/100)/1.050;
VGU = (1.44 *WT/100)/1.043;
VBO = (14.29*WT/100)/1.990;
VKI = (0.44 *WT/100)/1.050;
VAB = (2.81 *WT/100)/1.040;
VVB = (5.62 *WT/100)/1.040;
VRB = (3.86 *WT/100)/1.040;
## Fixed parameters
BP = 0.61; # Blood:plasma partition coefficient
fup = 0.028; # Fraction unbound in plasma
fub = fup/BP; # Fraction unbound in blood
KbLU = exp(0.8334);
KbHT = exp(1.1205);
KbSK = exp(-.5238);
KbSP = exp(0.3224);
KbPA = exp(0.3224);
KbLI = exp(1.7604);
KbST = exp(0.3224);
KbGU = exp(1.2026);
KbKI = exp(1.3171);
##-----------------------------------------
S15 = VVB*BP/1000;
C15 = Venous_Blood/S15
##-----------------------------------------
d/dt(Lungs) = QLU*(Venous_Blood/VVB - Lungs/KbLU/VLU);
d/dt(Heart) = QHT*(Arterial_Blood/VAB - Heart/KbHT/VHT);
d/dt(Brain) = QBR*(Arterial_Blood/VAB - Brain/KbBR/VBR);
d/dt(Muscles) = QMU*(Arterial_Blood/VAB - Muscles/KbMU/VMU);
d/dt(Adipose) = QAD*(Arterial_Blood/VAB - Adipose/KbAD/VAD);
d/dt(Skin) = QSK*(Arterial_Blood/VAB - Skin/KbSK/VSK);
d/dt(Spleen) = QSP*(Arterial_Blood/VAB - Spleen/KbSP/VSP);
d/dt(Pancreas) = QPA*(Arterial_Blood/VAB - Pancreas/KbPA/VPA);
d/dt(Liver) = QHA*Arterial_Blood/VAB + QSP*Spleen/KbSP/VSP + QPA*Pancreas/KbPA/VPA + QST*Stomach/KbST/VST + QGU*Gut/KbGU/VGU - CLint*fub*Liver/KbLI/VLI - QLI*Liver/KbLI/VLI;
d/dt(Stomach) = QST*(Arterial_Blood/VAB - Stomach/KbST/VST);
d/dt(Gut) = QGU*(Arterial_Blood/VAB - Gut/KbGU/VGU);
d/dt(Bones) = QBO*(Arterial_Blood/VAB - Bones/KbBO/VBO);
d/dt(Kidneys) = QKI*(Arterial_Blood/VAB - Kidneys/KbKI/VKI);
d/dt(Arterial_Blood) = QLU*(Lungs/KbLU/VLU - Arterial_Blood/VAB);
d/dt(Venous_Blood) = QHT*Heart/KbHT/VHT + QBR*Brain/KbBR/VBR + QMU*Muscles/KbMU/VMU + QAD*Adipose/KbAD/VAD + QSK*Skin/KbSK/VSK + QLI*Liver/KbLI/VLI + QBO*Bones/KbBO/VBO + QKI*Kidneys/KbKI/VKI + QRB*Rest_of_Body/KbRB/VRB - QLU*Venous_Blood/VVB;
d/dt(Rest_of_Body) = QRB*(Arterial_Blood/VAB - Rest_of_Body/KbRB/VRB);
})
If you look at the summary, you can see where RxODE assigned the compartment number(s)
summary(pbpk)
In this case, it is assigned to compartment 15. Figuring this out
can be inconvenient and also lead to re-numbering compartment in
simulation or estimation datasets. While it is easy and probably
clearer to specify the compartment by name, other
tools only support compartment numbers. Therefore, having a way to number
compartment easily can lead to less data modification between multiple
tools.
Changing compartment numbers by pre-declaring the compartments
To add the compartments to the RxODE model in the order you desire you
simply need to pre-declare the compartments with cmt. For example
specifying is Venous_Blood and Skin to be the 1st and 2nd
compartments, respectively, is simple:
pbpk2 <- RxODE({
cmt(Venous_Blood) ## Now this is the first compartment, ie cmt=1
cmt(Skin) ## Skin may be a compartment you wish to dose to as well, so it is now cmt=2
KbBR = exp(lKbBR)
KbMU = exp(lKbMU)
KbAD = exp(lKbAD)
CLint= exp(lCLint + eta.LClint)
KbBO = exp(lKbBO)
KbRB = exp(lKbRB)
## Regional blood flows
CO = (187.00*WT^0.81)*60/1000; # Cardiac output (L/h) from White et al (1968)
QHT = 4.0 *CO/100;
QBR = 12.0*CO/100;
QMU = 17.0*CO/100;
QAD = 5.0 *CO/100;
QSK = 5.0 *CO/100;
QSP = 3.0 *CO/100;
QPA = 1.0 *CO/100;
QLI = 25.5*CO/100;
QST = 1.0 *CO/100;
QGU = 14.0*CO/100;
QHA = QLI - (QSP + QPA + QST + QGU); # Hepatic artery blood flow
QBO = 5.0 *CO/100;
QKI = 19.0*CO/100;
QRB = CO - (QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI);
QLU = QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI + QRB;
## Organs' volumes = organs' weights / organs' density
VLU = (0.76 *WT/100)/1.051;
VHT = (0.47 *WT/100)/1.030;
VBR = (2.00 *WT/100)/1.036;
VMU = (40.00*WT/100)/1.041;
VAD = (21.42*WT/100)/0.916;
VSK = (3.71 *WT/100)/1.116;
VSP = (0.26 *WT/100)/1.054;
VPA = (0.14 *WT/100)/1.045;
VLI = (2.57 *WT/100)/1.040;
VST = (0.21 *WT/100)/1.050;
VGU = (1.44 *WT/100)/1.043;
VBO = (14.29*WT/100)/1.990;
VKI = (0.44 *WT/100)/1.050;
VAB = (2.81 *WT/100)/1.040;
VVB = (5.62 *WT/100)/1.040;
VRB = (3.86 *WT/100)/1.040;
## Fixed parameters
BP = 0.61; # Blood:plasma partition coefficient
fup = 0.028; # Fraction unbound in plasma
fub = fup/BP; # Fraction unbound in blood
KbLU = exp(0.8334);
KbHT = exp(1.1205);
KbSK = exp(-.5238);
KbSP = exp(0.3224);
KbPA = exp(0.3224);
KbLI = exp(1.7604);
KbST = exp(0.3224);
KbGU = exp(1.2026);
KbKI = exp(1.3171);
##-----------------------------------------
S15 = VVB*BP/1000;
C15 = Venous_Blood/S15
##-----------------------------------------
d/dt(Lungs) = QLU*(Venous_Blood/VVB - Lungs/KbLU/VLU);
d/dt(Heart) = QHT*(Arterial_Blood/VAB - Heart/KbHT/VHT);
d/dt(Brain) = QBR*(Arterial_Blood/VAB - Brain/KbBR/VBR);
d/dt(Muscles) = QMU*(Arterial_Blood/VAB - Muscles/KbMU/VMU);
d/dt(Adipose) = QAD*(Arterial_Blood/VAB - Adipose/KbAD/VAD);
d/dt(Skin) = QSK*(Arterial_Blood/VAB - Skin/KbSK/VSK);
d/dt(Spleen) = QSP*(Arterial_Blood/VAB - Spleen/KbSP/VSP);
d/dt(Pancreas) = QPA*(Arterial_Blood/VAB - Pancreas/KbPA/VPA);
d/dt(Liver) = QHA*Arterial_Blood/VAB + QSP*Spleen/KbSP/VSP + QPA*Pancreas/KbPA/VPA + QST*Stomach/KbST/VST + QGU*Gut/KbGU/VGU - CLint*fub*Liver/KbLI/VLI - QLI*Liver/KbLI/VLI;
d/dt(Stomach) = QST*(Arterial_Blood/VAB - Stomach/KbST/VST);
d/dt(Gut) = QGU*(Arterial_Blood/VAB - Gut/KbGU/VGU);
d/dt(Bones) = QBO*(Arterial_Blood/VAB - Bones/KbBO/VBO);
d/dt(Kidneys) = QKI*(Arterial_Blood/VAB - Kidneys/KbKI/VKI);
d/dt(Arterial_Blood) = QLU*(Lungs/KbLU/VLU - Arterial_Blood/VAB);
d/dt(Venous_Blood) = QHT*Heart/KbHT/VHT + QBR*Brain/KbBR/VBR + QMU*Muscles/KbMU/VMU + QAD*Adipose/KbAD/VAD + QSK*Skin/KbSK/VSK + QLI*Liver/KbLI/VLI + QBO*Bones/KbBO/VBO + QKI*Kidneys/KbKI/VKI + QRB*Rest_of_Body/KbRB/VRB - QLU*Venous_Blood/VVB;
d/dt(Rest_of_Body) = QRB*(Arterial_Blood/VAB - Rest_of_Body/KbRB/VRB);
})
You can see this change in the simple printout
pbpk2
The first two compartments are Venous_Blood followed by Skin.
Appending compartments to the model
You can also append "compartments" to the model. Because of the ODE
solving internals, you cannot add fake compartments to the model until
after all the differential equations are defined.
For example this is legal:
ode.1c.ka <- RxODE({
C2 = center/V;
d / dt(depot) = -KA * depot
d/dt(center) = KA * depot - CL*C2
cmt(eff);
})
print(ode.1c.ka)
Where as this is not:
ode.1c.ka <- RxODE({
cmt(eff);
C2 = center/V;
d / dt(depot) = -KA * depot
d/dt(center) = KA * depot - CL*C2
})
Which gives an error:
Error in rxModelVars_(obj) :
Evaluation error: Compartment 'eff' needs differential equations defined.
nlmixrdevelopment/RxODE.doc documentation built on Oct. 17, 2019, 1:27 a.m.
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How RxODE assigns compartment numbers
RxODE automatically assigns compartment numbers when parsing. For example, with the Mavoglurant PBPK model the following model may be used:
library(RxODE) pbpk <- RxODE({ KbBR = exp(lKbBR) KbMU = exp(lKbMU) KbAD = exp(lKbAD) CLint= exp(lCLint + eta.LClint) KbBO = exp(lKbBO) KbRB = exp(lKbRB) ## Regional blood flows CO = (187.00*WT^0.81)*60/1000; # Cardiac output (L/h) from White et al (1968) QHT = 4.0 *CO/100; QBR = 12.0*CO/100; QMU = 17.0*CO/100; QAD = 5.0 *CO/100; QSK = 5.0 *CO/100; QSP = 3.0 *CO/100; QPA = 1.0 *CO/100; QLI = 25.5*CO/100; QST = 1.0 *CO/100; QGU = 14.0*CO/100; QHA = QLI - (QSP + QPA + QST + QGU); # Hepatic artery blood flow QBO = 5.0 *CO/100; QKI = 19.0*CO/100; QRB = CO - (QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI); QLU = QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI + QRB; ## Organs' volumes = organs' weights / organs' density VLU = (0.76 *WT/100)/1.051; VHT = (0.47 *WT/100)/1.030; VBR = (2.00 *WT/100)/1.036; VMU = (40.00*WT/100)/1.041; VAD = (21.42*WT/100)/0.916; VSK = (3.71 *WT/100)/1.116; VSP = (0.26 *WT/100)/1.054; VPA = (0.14 *WT/100)/1.045; VLI = (2.57 *WT/100)/1.040; VST = (0.21 *WT/100)/1.050; VGU = (1.44 *WT/100)/1.043; VBO = (14.29*WT/100)/1.990; VKI = (0.44 *WT/100)/1.050; VAB = (2.81 *WT/100)/1.040; VVB = (5.62 *WT/100)/1.040; VRB = (3.86 *WT/100)/1.040; ## Fixed parameters BP = 0.61; # Blood:plasma partition coefficient fup = 0.028; # Fraction unbound in plasma fub = fup/BP; # Fraction unbound in blood KbLU = exp(0.8334); KbHT = exp(1.1205); KbSK = exp(-.5238); KbSP = exp(0.3224); KbPA = exp(0.3224); KbLI = exp(1.7604); KbST = exp(0.3224); KbGU = exp(1.2026); KbKI = exp(1.3171); ##----------------------------------------- S15 = VVB*BP/1000; C15 = Venous_Blood/S15 ##----------------------------------------- d/dt(Lungs) = QLU*(Venous_Blood/VVB - Lungs/KbLU/VLU); d/dt(Heart) = QHT*(Arterial_Blood/VAB - Heart/KbHT/VHT); d/dt(Brain) = QBR*(Arterial_Blood/VAB - Brain/KbBR/VBR); d/dt(Muscles) = QMU*(Arterial_Blood/VAB - Muscles/KbMU/VMU); d/dt(Adipose) = QAD*(Arterial_Blood/VAB - Adipose/KbAD/VAD); d/dt(Skin) = QSK*(Arterial_Blood/VAB - Skin/KbSK/VSK); d/dt(Spleen) = QSP*(Arterial_Blood/VAB - Spleen/KbSP/VSP); d/dt(Pancreas) = QPA*(Arterial_Blood/VAB - Pancreas/KbPA/VPA); d/dt(Liver) = QHA*Arterial_Blood/VAB + QSP*Spleen/KbSP/VSP + QPA*Pancreas/KbPA/VPA + QST*Stomach/KbST/VST + QGU*Gut/KbGU/VGU - CLint*fub*Liver/KbLI/VLI - QLI*Liver/KbLI/VLI; d/dt(Stomach) = QST*(Arterial_Blood/VAB - Stomach/KbST/VST); d/dt(Gut) = QGU*(Arterial_Blood/VAB - Gut/KbGU/VGU); d/dt(Bones) = QBO*(Arterial_Blood/VAB - Bones/KbBO/VBO); d/dt(Kidneys) = QKI*(Arterial_Blood/VAB - Kidneys/KbKI/VKI); d/dt(Arterial_Blood) = QLU*(Lungs/KbLU/VLU - Arterial_Blood/VAB); d/dt(Venous_Blood) = QHT*Heart/KbHT/VHT + QBR*Brain/KbBR/VBR + QMU*Muscles/KbMU/VMU + QAD*Adipose/KbAD/VAD + QSK*Skin/KbSK/VSK + QLI*Liver/KbLI/VLI + QBO*Bones/KbBO/VBO + QKI*Kidneys/KbKI/VKI + QRB*Rest_of_Body/KbRB/VRB - QLU*Venous_Blood/VVB; d/dt(Rest_of_Body) = QRB*(Arterial_Blood/VAB - Rest_of_Body/KbRB/VRB); })
If you look at the summary, you can see where RxODE assigned the compartment number(s)
summary(pbpk)
In this case, it is assigned to compartment 15. Figuring this out
can be inconvenient and also lead to re-numbering compartment in
simulation or estimation datasets. While it is easy and probably
clearer to specify the compartment by name, other
tools only support compartment numbers. Therefore, having a way to number
compartment easily can lead to less data modification between multiple
tools.
Changing compartment numbers by pre-declaring the compartments
To add the compartments to the RxODE model in the order you desire you
simply need to pre-declare the compartments with cmt. For example
specifying is Venous_Blood and Skin to be the 1st and 2nd
compartments, respectively, is simple:
pbpk2 <- RxODE({ cmt(Venous_Blood) ## Now this is the first compartment, ie cmt=1 cmt(Skin) ## Skin may be a compartment you wish to dose to as well, so it is now cmt=2 KbBR = exp(lKbBR) KbMU = exp(lKbMU) KbAD = exp(lKbAD) CLint= exp(lCLint + eta.LClint) KbBO = exp(lKbBO) KbRB = exp(lKbRB) ## Regional blood flows CO = (187.00*WT^0.81)*60/1000; # Cardiac output (L/h) from White et al (1968) QHT = 4.0 *CO/100; QBR = 12.0*CO/100; QMU = 17.0*CO/100; QAD = 5.0 *CO/100; QSK = 5.0 *CO/100; QSP = 3.0 *CO/100; QPA = 1.0 *CO/100; QLI = 25.5*CO/100; QST = 1.0 *CO/100; QGU = 14.0*CO/100; QHA = QLI - (QSP + QPA + QST + QGU); # Hepatic artery blood flow QBO = 5.0 *CO/100; QKI = 19.0*CO/100; QRB = CO - (QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI); QLU = QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI + QRB; ## Organs' volumes = organs' weights / organs' density VLU = (0.76 *WT/100)/1.051; VHT = (0.47 *WT/100)/1.030; VBR = (2.00 *WT/100)/1.036; VMU = (40.00*WT/100)/1.041; VAD = (21.42*WT/100)/0.916; VSK = (3.71 *WT/100)/1.116; VSP = (0.26 *WT/100)/1.054; VPA = (0.14 *WT/100)/1.045; VLI = (2.57 *WT/100)/1.040; VST = (0.21 *WT/100)/1.050; VGU = (1.44 *WT/100)/1.043; VBO = (14.29*WT/100)/1.990; VKI = (0.44 *WT/100)/1.050; VAB = (2.81 *WT/100)/1.040; VVB = (5.62 *WT/100)/1.040; VRB = (3.86 *WT/100)/1.040; ## Fixed parameters BP = 0.61; # Blood:plasma partition coefficient fup = 0.028; # Fraction unbound in plasma fub = fup/BP; # Fraction unbound in blood KbLU = exp(0.8334); KbHT = exp(1.1205); KbSK = exp(-.5238); KbSP = exp(0.3224); KbPA = exp(0.3224); KbLI = exp(1.7604); KbST = exp(0.3224); KbGU = exp(1.2026); KbKI = exp(1.3171); ##----------------------------------------- S15 = VVB*BP/1000; C15 = Venous_Blood/S15 ##----------------------------------------- d/dt(Lungs) = QLU*(Venous_Blood/VVB - Lungs/KbLU/VLU); d/dt(Heart) = QHT*(Arterial_Blood/VAB - Heart/KbHT/VHT); d/dt(Brain) = QBR*(Arterial_Blood/VAB - Brain/KbBR/VBR); d/dt(Muscles) = QMU*(Arterial_Blood/VAB - Muscles/KbMU/VMU); d/dt(Adipose) = QAD*(Arterial_Blood/VAB - Adipose/KbAD/VAD); d/dt(Skin) = QSK*(Arterial_Blood/VAB - Skin/KbSK/VSK); d/dt(Spleen) = QSP*(Arterial_Blood/VAB - Spleen/KbSP/VSP); d/dt(Pancreas) = QPA*(Arterial_Blood/VAB - Pancreas/KbPA/VPA); d/dt(Liver) = QHA*Arterial_Blood/VAB + QSP*Spleen/KbSP/VSP + QPA*Pancreas/KbPA/VPA + QST*Stomach/KbST/VST + QGU*Gut/KbGU/VGU - CLint*fub*Liver/KbLI/VLI - QLI*Liver/KbLI/VLI; d/dt(Stomach) = QST*(Arterial_Blood/VAB - Stomach/KbST/VST); d/dt(Gut) = QGU*(Arterial_Blood/VAB - Gut/KbGU/VGU); d/dt(Bones) = QBO*(Arterial_Blood/VAB - Bones/KbBO/VBO); d/dt(Kidneys) = QKI*(Arterial_Blood/VAB - Kidneys/KbKI/VKI); d/dt(Arterial_Blood) = QLU*(Lungs/KbLU/VLU - Arterial_Blood/VAB); d/dt(Venous_Blood) = QHT*Heart/KbHT/VHT + QBR*Brain/KbBR/VBR + QMU*Muscles/KbMU/VMU + QAD*Adipose/KbAD/VAD + QSK*Skin/KbSK/VSK + QLI*Liver/KbLI/VLI + QBO*Bones/KbBO/VBO + QKI*Kidneys/KbKI/VKI + QRB*Rest_of_Body/KbRB/VRB - QLU*Venous_Blood/VVB; d/dt(Rest_of_Body) = QRB*(Arterial_Blood/VAB - Rest_of_Body/KbRB/VRB); })
You can see this change in the simple printout
pbpk2
The first two compartments are Venous_Blood followed by Skin.
Appending compartments to the model
You can also append "compartments" to the model. Because of the ODE solving internals, you cannot add fake compartments to the model until after all the differential equations are defined.
For example this is legal:
ode.1c.ka <- RxODE({ C2 = center/V; d / dt(depot) = -KA * depot d/dt(center) = KA * depot - CL*C2 cmt(eff); }) print(ode.1c.ka)
Where as this is not:
ode.1c.ka <- RxODE({ cmt(eff); C2 = center/V; d / dt(depot) = -KA * depot d/dt(center) = KA * depot - CL*C2 })
Which gives an error:
Error in rxModelVars_(obj) : Evaluation error: Compartment 'eff' needs differential equations defined.
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