ff.PKPD.1.comp.sd.CL.emax: Structural model: one-compartment, single bolus IV dose,...

In PopED: Population (and Individual) Optimal Experimental Design

Structural model: one-compartment, single bolus IV dose, parameterized using CL driving an EMAX model with a direct effect.

Description

This is a structural model function that encodes the model described above. The function is suitable for input to the create.poped.database function using the ff_fun or ff_file argument.

Usage

ff.PKPD.1.comp.sd.CL.emax(model_switch, xt, parameters, poped.db)

Arguments

model_switch	a vector of values, the same size as xt, identifying which model response should be computed for the corresponding xt value. Used for multiple response models.
xt	a vector of independent variable values (often time).
parameters	A named list of parameter values.
poped.db	a poped database. This can be used to extract information that may be needed in the model file.

Value

A list consisting of:

1. y the values of the model at the specified points.

2. poped.db A (potentially modified) poped database.

See Also

Other models: feps.add(), feps.add.prop(), feps.prop(), ff.PK.1.comp.oral.md.CL(), ff.PK.1.comp.oral.md.KE(), ff.PK.1.comp.oral.sd.CL(), ff.PK.1.comp.oral.sd.KE(), ff.PKPD.1.comp.oral.md.CL.imax()

Other structural_models: ff.PK.1.comp.oral.md.CL(), ff.PK.1.comp.oral.md.KE(), ff.PK.1.comp.oral.sd.CL(), ff.PK.1.comp.oral.sd.KE(), ff.PKPD.1.comp.oral.md.CL.imax()

Examples

library(PopED)

## find the parameters that are needed to define from the structural model
ff.PKPD.1.comp.sd.CL.emax

## -- parameter definition function 
## -- names match parameters in function ff
sfg <- function(x,a,bpop,b,bocc){
  ## -- parameter definition function
  parameters=c( 
    CL=bpop[1]*exp(b[1])  ,
    V=bpop[2]*exp(b[2])  ,
    E0=bpop[3]*exp(b[3])  ,
    EMAX=bpop[4]*exp(b[4])	,
    EC50=bpop[5]*exp(b[5])	,
    DOSE=a[1]
  )
  return( parameters ) 
}

feps <- function(model_switch,xt,parameters,epsi,poped.db){
  ## -- Residual Error function
  ## -- Proportional PK + additive PD
  returnArgs <- do.call(poped.db$model$ff_pointer,list(model_switch,xt,parameters,poped.db)) 
  y <- returnArgs[[1]]
  poped.db <- returnArgs[[2]]
  
  MS <- model_switch
  
  prop.err <- y*(1+epsi[,1])
  add.err <- y+epsi[,2]
  
  y[MS==1] = prop.err[MS==1]
  y[MS==2] = add.err[MS==2]
  
  return(list( y= y,poped.db =poped.db )) 
}

## -- Define initial design  and design space
poped.db <- create.poped.database(ff_fun=ff.PKPD.1.comp.sd.CL.emax,
                                  fError_fun=feps,
                                  fg_fun=sfg,
                                  groupsize=20,
                                  m=3,
                                  sigma=diag(c(0.15,0.15)),
                                  bpop=c(CL=0.5,V=0.2,E0=1,EMAX=1,EC50=1),  
                                  d=c(CL=0.01,V=0.01,E0=0.01,EMAX=0.01,EC50=0.01), 
                                  xt=c( 0.33,0.66,0.9,5,0.1,1,2,5),
                                  model_switch=c( 1,1,1,1,2,2,2,2),
                                  minxt=0,
                                  maxxt=5,
                                  a=rbind(2.75,5,10),
                                  bUseGrouped_xt=1,
                                  maxa=10,
                                  mina=0.1)


##  create plot of model without variability 
plot_model_prediction(poped.db,facet_scales="free")

## evaluate initial design
FIM <- evaluate.fim(poped.db) 
FIM
det(FIM)
get_rse(FIM,poped.db)

PopED documentation built on Oct. 8, 2024, 1:07 a.m.