Hi guys, Just learning to simulate with Julia codes and build model libraries. I have written a Non linear model for Phenytoin, Can someone verify if this is modeled correctly? A doubt I have is with entering Vmax values : if we dose the drug every 24 hours does the Vmax value need to be in mg/hr or mg/day?

## title : Phenytoin - Non Linear Model

```
using Pumas
using Plots
```

Model Development

```
phenytoin = @model begin
@param begin
θ ∈ VectorDomain(4)
end
@pre begin
Vc = θ[1]
Ka = θ[2]
Vmax = θ[3]
Km = θ[4]
end
@vars begin
Cp := Central/Vc
end
@dynamics begin
Depot' = -Ka*Depot
Central' = Ka*Depot - Vmax*Cp/(Km+Cp)
end
@derived begin
cp = @. Central/Vc
end
end
```

- A subject of 80kg is administered Phenytoin at population values of Vmax=7mg/kg/day (560mg/day, converted to 23.33mg/hr) and Km=5mg/L to achieve Cpave=15mg/L but the Cpave was found to be 20mg/L(figure=2).

```
regimen4 = DosageRegimen([600,140], time=[0,0], cmt=[2,1], addl=[0,55], ii=[0,8])
subject4 = Subject(id=1, evs=regimen4)
param4 = (θ = [42,1,23.33,4.94],)
sim4 = simobs(phenytoin, subject4, param4, obstimes=0:0.1:500)
plot(sim4)
```

- The Vmax was then calcuated for the patient and the simulation was carried out which showed the Cpave=20mg/L.

```
regimen5 = DosageRegimen([600,140], time=[0,0], cmt=[2,1], addl=[0,55], ii=[0,8])
subject5 = Subject(id=1, evs=regimen5)
param5 = (θ = [42,1,21.875,4.94],)
sim5 = simobs(phenytoin, subject5, param5, obstimes=0:0.1:500)
plot(sim5)
```

- A new dosing regimen to achieve the Cpave=15mg/L at the patient specific Vmax is shown below:

```
regimen6 = DosageRegimen([600,132], time=[0,0], cmt=[2,1], addl=[0,55], ii=[0,8])
subject6 = Subject(id=1, evs=regimen6)
param6 = (θ = [42,1,21.875,4.94],)
sim6 = simobs(phenytoin, subject6, param6, obstimes=0:0.1:500)
plot(sim6)
```