Unrealistic simulations simulations

  • a3bdu3
    Member
    10

    #3928

    Hi,

    I am trying to simulate time concentration profiles for a drug given by IV infusion that follows a 2 compartment model. When residual variability is included in the model the simulation results are unrealistic and not near my original observations.

    This happens whether I am simulating using Monolix or Simulx/mlxr in R. Below is an example for the r code I used to simulate time concentration profiles with mlxr:

    pk.model <- inlineModel(”
    [LONGITUDINAL]
    input = {V1, Cl, Q, V2, b}

    PK:
    compartment(concentration=Cc, volume=V1)
    iv()
    peripheral(k12 = Q/V1, k21 = Q/V2, amount=Ap, volume=V2, concentration=Cp)
    elimination(k=Cl/V1)
    DEFINITION:
    y1 = {distribution=lognormal, prediction=Cc, errorModel=proportional(b)}

    [INDIVIDUAL]
    input={V1_pop, omega_V1, Cl_pop, omega_Cl, Q_pop, omega_Q,V2_pop, omega_V2}
    DEFINITION:
    V1 = {distribution=lognormal, prediction=V1_pop, sd=omega_V1}
    Cl = {distribution=lognormal, prediction=Cl_pop, sd=omega_Cl}
    Q = {distribution=lognormal, prediction=Q_pop, sd=omega_Q}
    V2 = {distribution=lognormal, prediction=V2_pop, sd=omega_V2}

    output = Cc
    “)

    adm <- list(time=seq(0,to=24,by=24), amount=400,rate=400)

    ppk <- c(V1_pop=33.1, Cl_pop=3.96, Q_pop=7,V2_pop=48.3,
    omega_V1=0.36, omega_Cl=0.4, omega_Q=0.72,omega_V2=0.00001, b=0.23)

    g <- list(size=2, level=’individual’)

    y1 <- list(name=’y1′, time=seq(0,to=24,by=0.5))

    s <- list(seed=1234)

    res1 <- simulx(model = pk.model,
    parameter = ppk,
    treatment = adm,
    group = g,
    output = list(y1),
    settings = s)

    res1$y1
    id time y1
    1 1 0.0 0.0000000
    2 1 0.5 2.1235770
    3 1 1.0 26.7305542
    4 1 1.5 14.5429178
    5 1 2.0 5.1720819
    6 1 2.5 29.0014866
    7 1 3.0 3.1412130

    The predicted concentrations are not realistic, and I get similar results when I used Monolix to simulate
    Is Their something wrong I am doing or is it a problem with Monolix, because I never had this issue with the earlier version of Monolix

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a3bdu3Unrealistic simulations simulations