library(PopED)
##-- Model: One comp first order absorption
library(Rcpp)
cppFunction(
'List one_comp_oral_ode(double Time, NumericVector A, NumericVector Pars) {
int n = A.size();
NumericVector dA(n);
double CL_OCC_1 = Pars[0];
double CL_OCC_2 = Pars[1];
double V = Pars[2];
double KA = Pars[3];
double TAU = Pars[4];
double N,CL;
N = floor(Time/TAU)+1;
CL = CL_OCC_1;
if(N>6) CL = CL_OCC_2;
dA[0] = -KA*A[0];
dA[1] = KA*A[0] - (CL/V)*A[1];
return List::create(dA);
}'
)
ff.ode.rcpp <- function(model_switch, xt, parameters, poped.db){
with(as.list(parameters),{
A_ini <- c(A1=0, A2=0)
times_xt <- drop(xt) #xt[,,drop=T]
dose_times = seq(from=0,to=max(times_xt),by=TAU)
eventdat <- data.frame(var = c("A1"),
time = dose_times,
value = c(DOSE), method = c("add"))
times <- sort(c(times_xt,dose_times))
out <- ode(A_ini, times, one_comp_oral_ode, c(CL_OCC_1,CL_OCC_2,V,KA,TAU),
events = list(data = eventdat))#atol=1e-13,rtol=1e-13)
y = out[, "A2"]/(V)
y=y[match(times_xt,out[,"time"])]
y=cbind(y)
return(list(y=y,poped.db=poped.db))
})
}
## -- parameter definition function
## -- names match parameters in function ff
sfg <- function(x,a,bpop,b,bocc){
parameters=c( CL_OCC_1=bpop[1]*exp(b[1]+bocc[1,1]),
CL_OCC_2=bpop[1]*exp(b[1]+bocc[1,2]),
V=bpop[2]*exp(b[2]),
KA=bpop[3]*exp(b[3]),
DOSE=a[1],
TAU=a[2])
return( parameters )
}
## -- Define design and design space
poped.db <- create.poped.database(ff_fun=ff.ode.rcpp,
fError_fun=feps.add.prop,
fg_fun=sfg,
bpop=c(CL=3.75,V=72.8,KA=0.25),
d=c(CL=0.25^2,V=0.09,KA=0.09),
sigma=c(0.04,5e-6),
notfixed_sigma=c(0,0),
docc = matrix(c(0,0.09,0),nrow = 1),
m=2,
groupsize=20,
xt=c( 1,2,8,240,245),
minxt=c(0,0,0,240,240),
maxxt=c(10,10,10,248,248),
bUseGrouped_xt=1,
a=list(c(DOSE=20,TAU=24),c(DOSE=40, TAU=24)),
maxa=c(DOSE=200,TAU=24),
mina=c(DOSE=0,TAU=24))
## create plot of model without variability
plot_model_prediction(poped.db, model_num_points = 300)
## Visulaize the IOV
library(ggplot2)
set.seed(12345679)
plot_model_prediction(poped.db, PRED=F,IPRED=F,
separate.groups=T, model_num_points = 500,
groupsize_sim = 1,
IPRED.lines = T, alpha.IPRED.lines=0.6,
sample.times = F
) + geom_vline(xintercept = 24*6,color="red")
## evaluate initial design
evaluate_design(poped.db)
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