if (campsis::onCran()) { cat("This vignette was not built on CRAN. Please check out the online version [here](https://calvagone.github.io/campsis.doc/articles/v06_infusions.html).") knitr::knit_exit() }
library(campsis)
There are 2 ways to implement infusions in CAMPSIS:
In the first case, the simulation engine will take care of the infusion duration or rate (RATE in dataset will be -1 or -2). In the second case, CAMPSIS will inject specific values in the RATE column of the dataset.
Let's use a 2-compartment model without absorption compartment to illustrate how this can be achieved.
model <- model_suite$nonmem$advan3_trans4
For this example, we're going to define a lag time D1
for this absorption compartment.
First let's create a new parameter D1
, log-normally distributed with a median of 5 hours and 20% CV.
model <- model %>% add(Theta(name="D1", value=5)) model <- model %>% add(Omega(name="D1", value=20, type="cv%"))
Now, let's add an equation to the drug model to define D1
.
model <- model %>% add(Equation("D1", "THETA_D1*exp(ETA_D1)"))
Finally, we need to tell CAMPSIS that D1
corresponds the infusion duration for the first compartment.
model <- model %>% add(InfusionDuration(compartment=1, rhs="D1"))
Our persisted drug model would look like this:
model
Now, let's infuse 1000 mg and run the simulation.
ds1 <- Dataset(50) %>% add(Infusion(time=0, amount=1000)) %>% add(Observations(times=seq(0,24,by=0.5)))
results_d1 <- model %>% simulate(dataset=ds1, seed=1) shadedPlot(results_d1, "CONC")
The same simulation can be performed by defining the infusion duration in the dataset.
For this, we need to sample D1
values. This can be done as follows:
set.seed(1)
distribution <- ParameterDistribution(model=model, theta="D1", omega="D1") %>% sample(50L)
We can then pass the pre-sampled distribution.
ds2 <- Dataset(50) %>% add(Infusion(time=0, amount=1000, duration=distribution)) %>% add(Observations(times=seq(0,24,by=0.5)))
Here is an overview of the dataset in its table form if we filter on the doses:
ds2 %>% export(dest="RxODE") %>% dosingOnly() %>% head()
Let's now simulate this dataset using the original model.
results_d1 <- model_suite$nonmem$advan4_trans4 %>% simulate(dataset=ds2, seed=1) shadedPlot(results_d1, "CONC")
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