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
phenytoin = @model begin @param begin θ ∈ VectorDomain(4) end @pre begin Vc = θ Ka = θ Vmax = θ Km = θ 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)