In nlmixr2/rxode2: Facilities for Simulating from ODE-Based Models

rxode2 automatically assigns compartment numbers when parsing. For example, with the Mavoglurant PBPK model the following model may be used:

library(rxode2)

pbpk <- function() {
  model({
    KbBR = exp(lKbBR)
    KbMU = exp(lKbMU)
    KbAD = exp(lKbAD)
    CLint= exp(lCLint + eta.LClint)
    KbBO = exp(lKbBO)
    KbRB = exp(lKbRB)

    ## Regional blood flows
    # Cardiac output (L/h) from White et al (1968)
    CO  = (187.00*WT^0.81)*60/1000 
    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
    # Hepatic artery blood flow
    QHA = QLI - (QSP + QPA + QST + QGU) 
    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 printout, you can see where rxode2 assigned the compartment number(s)

pbpk <- pbpk()
print(pbpk)

You can also see this with the classic rxode2 model. In that case you use the summary() function:

pbpk <- pbpk$simulationModel
summary(pbpk)

In this case, Venous_Blood 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.

nlmixr2/rxode2 documentation built on Jan. 11, 2025, 8:48 a.m.