Chapter 6 RxODE syntax

This briefly describes the syntax used to define models that RxODE will translate into R-callable compiled code. It also describes the communication of variables between R and the RxODE modeling specification.

6.1 Example

   # An RxODE model specification (this line is a comment).

   if(comed==0){   # concomitant medication (con-med)?
      F = 1.0;     # full bioavailability w.o. con-med
   }
   else {
      F = 0.80;    # 20% reduced bioavailability
   }

   C2 = centr/V2;  # concentration in the central compartment
   C3 = peri/V3;   # concentration in the peripheral compartment

   # ODE describing the PK and PD

   d/dt(depot) = -KA*depot;
   d/dt(centr) = F*KA*depot - CL*C2 - Q*C2 + Q*C3;
   d/dt(peri)  =                      Q*C2 - Q*C3;
   d/dt(eff)   = Kin - Kout*(1-C2/(EC50+C2))*eff;

6.2 Syntax

An RxODE model specification consists of one or more statements optionally terminated by semi-colons ; and optional comments (comments are delimited by # and an end-of-line).

A block of statements is a set of statements delimited by curly braces, { ... }.

Statements can be either assignments, conditional if/else if/else, while loops (can be exited by break), special statements, or printing statements (for debugging/testing)

Assignment statements can be:

  • simple assignments, where the left hand is an identifier (i.e., variable)

  • special time-derivative assignments, where the left hand specifies the change of the amount in the corresponding state variable (compartment) with respect to time e.g., d/dt(depot):

  • special initial-condition assignments where the left hand specifies the compartment of the initial condition being specified, e.g. depot(0) = 0

  • special model event changes including bioavailability (f(depot)=1), lag time (alag(depot)=0), modeled rate (rate(depot)=2) and modeled duration (dur(depot)=2). An example of these model features and the event specification for the modeled infusions the RxODE data specification is found in RxODE events section.

  • special change point syntax, or model times. These model times are specified by mtime(var)=time

  • special Jacobian-derivative assignments, where the left hand specifies the change in the compartment ode with respect to a variable. For example, if d/dt(y) = dy, then a Jacobian for this compartment can be specified as df(y)/dy(dy) = 1. There may be some advantage to obtaining the solution or specifying the Jacobian for very stiff ODE systems. However, for the few stiff systems we tried with LSODA, this actually slightly slowed down the solving.

Note that assignment can be done by =, <- or ~.

When assigning with the ~ operator, the simple assignments and time-derivative assignments will not be output.

Special statements can be:

  • Compartment declaration statements, which can change the default dosing compartment and the assumed compartment number(s) as well as add extra compartment names at the end (useful for multiple-endpoint nlmixr models); These are specified by cmt(compartmentName)

  • Parameter declaration statements, which can make sure the input parameters are in a certain order instead of ordering the parameters by the order they are parsed. This is useful for keeping the parameter order the same when using 2 different ODE models. These are specified by param(par1, par2,...)

An example model is shown below:

   # simple assignment
   C2 = centr/V2;

   # time-derivative assignment
   d/dt(centr) = F*KA*depot - CL*C2 - Q*C2 + Q*C3;

Expressions in assignment and if statements can be numeric or logical, however, no character nor integer expressions are currently supported.

Numeric expressions can include the following numeric operators +, -, *, /, ^ and those mathematical functions defined in the C or the R math libraries (e.g., fabs, exp, log, sin, abs).

You may also access the R’s functions in the R math libraries, like lgammafn for the log gamma function.

The RxODE syntax is case-sensitive, i.e., ABC is different than abc, Abc, ABc, etc.

6.2.1 Identifiers

Like R, Identifiers (variable names) may consist of one or more alphanumeric, underscore _ or period . characters, but the first character cannot be a digit or underscore _.

Identifiers in a model specification can refer to:

  • State variables in the dynamic system (e.g., compartments in a pharmacokinetics model).
  • Implied input variable, t (time), tlast (last time point), and podo (oral dose, in the undocumented case of absorption transit models).
  • Special constants like pi or R’s predefined constants.
  • Model parameters (e.g., ka rate of absorption, CL clearance, etc.)
  • Others, as created by assignments as part of the model specification; these are referred as LHS (left-hand side) variable.

Currently, the RxODE modeling language only recognizes system state variables and “parameters”, thus, any values that need to be passed from R to the ODE model (e.g., age) should be either passed in the params argument of the integrator function rxSolve() or be in the supplied event data-set.

There are certain variable names that are in the RxODE event tables. To avoid confusion, the following event table-related items cannot be assigned, or used as a state but can be accessed in the RxODE code:

  • cmt
  • dvid
  • addl
  • ss
  • rate
  • id

However the following variables are cannot be used in a model specification:

  • evid
  • ii

Sometimes RxODE generates variables that are fed back to RxODE. Similarly, nlmixr generates some variables that are used in nlmixr estimation and simulation. These variables start with the either the rx or nlmixr prefixes. To avoid any problems, it is suggested to not use these variables starting with either the rx or nlmixr prefixes.

6.3 Logical Operators

Logical operators support the standard R operators ==, != >= <= > and <. Like R these can be in if() or while() statements, ifelse() expressions. Additionally they can be in a standard assignment. For instance, the following is valid:

cov1 = covm*(sexf == "female") + covm*(sexf != "female")

Notice that you can also use character expressions in comparisons. This convenience comes at a cost since character comparisons are slower than numeric expressions. Unlike R, as.numeric or as.integer for these logical statements is not only not needed, but will cause an syntax error if you try to use the function.

6.4 cmt() changing compartment numbers for states

The compartment order can be changed with the cmt() syntax in the model. To understand what the cmt() can do you need to understand how RxODE numbers the compartments.

Below is an example of how RxODE numbers compartments

6.4.1 How RxODE numbers compartments

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
    # 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 summary, you can see where RxODE assigned the compartment number(s)

summary(pbpk)
#> RxODE 1.0.5 model named rx_74372d99e4c72628e9dee8939b90cb49 model (✔ ready). 
#> DLL: /home/matt/.cache/R/RxODE/rx_74372d99e4c72628e9dee8939b90cb49__.rxd/rx_74372d99e4c72628e9dee8939b90cb49_.so
#> NULL
#> 
#> Calculated Variables:
#>  [1] "KbBR"  "KbMU"  "KbAD"  "CLint" "KbBO"  "KbRB"  "CO"    "QHT"   "QBR"  
#> [10] "QMU"   "QAD"   "QSK"   "QSP"   "QPA"   "QLI"   "QST"   "QGU"   "QHA"  
#> [19] "QBO"   "QKI"   "QRB"   "QLU"   "VLU"   "VHT"   "VBR"   "VMU"   "VAD"  
#> [28] "VSK"   "VSP"   "VPA"   "VLI"   "VST"   "VGU"   "VBO"   "VKI"   "VAB"  
#> [37] "VVB"   "VRB"   "fub"   "KbLU"  "KbHT"  "KbSK"  "KbSP"  "KbPA"  "KbLI" 
#> [46] "KbST"  "KbGU"  "KbKI"  "S15"   "C15"  
#> ▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂ RxODE Model Syntax ▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂
#> RxODE({
#>     KbBR = exp(lKbBR)
#>     KbMU = exp(lKbMU)
#>     KbAD = exp(lKbAD)
#>     CLint = exp(lCLint + eta.LClint)
#>     KbBO = exp(lKbBO)
#>     KbRB = exp(lKbRB)
#>     CO = (187 * WT^0.81) * 60/1000
#>     QHT = 4 * CO/100
#>     QBR = 12 * CO/100
#>     QMU = 17 * CO/100
#>     QAD = 5 * CO/100
#>     QSK = 5 * CO/100
#>     QSP = 3 * CO/100
#>     QPA = 1 * CO/100
#>     QLI = 25.5 * CO/100
#>     QST = 1 * CO/100
#>     QGU = 14 * CO/100
#>     QHA = QLI - (QSP + QPA + QST + QGU)
#>     QBO = 5 * CO/100
#>     QKI = 19 * CO/100
#>     QRB = CO - (QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI)
#>     QLU = QHT + QBR + QMU + QAD + QSK + QLI + QBO + QKI + QRB
#>     VLU = (0.76 * WT/100)/1.051
#>     VHT = (0.47 * WT/100)/1.03
#>     VBR = (2 * WT/100)/1.036
#>     VMU = (40 * 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)/1.04
#>     VST = (0.21 * WT/100)/1.05
#>     VGU = (1.44 * WT/100)/1.043
#>     VBO = (14.29 * WT/100)/1.99
#>     VKI = (0.44 * WT/100)/1.05
#>     VAB = (2.81 * WT/100)/1.04
#>     VVB = (5.62 * WT/100)/1.04
#>     VRB = (3.86 * WT/100)/1.04
#>     BP = 0.61
#>     fup = 0.028
#>     fub = fup/BP
#>     KbLU = exp(0.8334)
#>     KbHT = exp(1.1205)
#>     KbSK = exp(-0.5238)
#>     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)
#> }) 
#> ▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂

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.

6.4.2 Changing compartments by pre-declaring with cmt()

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({
  ## Now this is the first compartment, ie cmt=1
  cmt(Venous_Blood)
  ## Skin may be a compartment you wish to dose to as well,
  ##  so it is now cmt=2
  cmt(Skin) 
  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)m
  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;
  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
#> RxODE 1.0.5 model named rx_a65bdb529b0485f601cec6187b5faaf5 model (✔ ready). 
#> x$state: Venous_Blood, Skin, Lungs, Heart, Brain, Muscles, Adipose, Spleen, Pancreas, Liver, Stomach, Gut, Bones, Kidneys, Arterial_Blood, Rest_of_Body
#> x$params: lKbBR, lKbMU, lKbAD, lCLint, eta.LClint, lKbBO, lKbRB, WT, BP, fup
#> x$lhs: KbBR, KbMU, KbAD, CLint, KbBO, KbRB, CO, QHT, QBR, QMU, QAD, QSK, QSP, QPA, QLI, QST, QGU, QHA, QBO, QKI, QRB, QLU, VLU, VHT, VBR, VMU, VAD, VSK, VSP, VPA, VLI, VST, VGU, VBO, VKI, VAB, VVB, VRB, fub, KbLU, KbHT, KbSK, KbSP, KbPA, KbLI, KbST, KbGU, KbKI, S15, C15

The first two compartments are Venous_Blood followed by Skin.

6.4.3 Appending compartments to the model with cmt()

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)
#> RxODE 1.0.5 model named rx_47c1eb3facce5268a288e5652999299e model (✔ ready). 
#> $state: depot, center
#> $stateExtra: eff
#> $params: V, KA, CL
#> $lhs: C2

But compartments defined before all the differential equations is not supported; So the model below:

ode.1c.ka <- RxODE({
    cmt(eff);
    C2 = center/V;
    d / dt(depot) = -KA * depot
    d/dt(center) = KA * depot - CL*C2
})

will give an error:

Error in rxModelVars_(obj) : 
  Evaluation error: Compartment 'eff' needs differential equations defined.