Structural model - Two compartment linear elimination with zero order absorption
Route of administration - Three consecutive constant rate IV infusion
Dosage Regimen - 1st dose:- 26.9 mcg/kg over 15min, 2nd dose:- 139 mcg/kg from 15min to 8hr, 3rd dose:- 138.95 mcg/kg between 8hr to 24hr
Number of Subjects - 1
In this model you will learn how to build a two compartment model and simulate for a single subject.
Call the "necessary" libraries to get start.
using Random using Pumas using PumasUtilities using CairoMakie
In this two compartment model we administer three consecutive IV infusion for a single subject and we assess the disposition of drug and fitting the model to the observed data.
pk_39 = @model begin @metadata begin desc = "Two Compartment Model" timeu = u"hr" end @param begin "Clearance (L/kg/hr)" tvcl ∈ RealDomain(lower=0) "Volume of Central Compartment (L/kg)" tvvc ∈ RealDomain(lower=0) "Volume of Peripheral Compartment (L/kg)" tvvp ∈ RealDomain(lower=0) "Intercompartmental clearance (L/kg/hr)" tvq ∈ RealDomain(lower=0) Ω ∈ PDiagDomain(4) "Proportional RUV" σ²_prop ∈ RealDomain(lower=0) end @random begin η ~ MvNormal(Ω) end @pre begin CL = tvcl * exp(η) Vc = tvvc * exp(η) Vp = tvvp * exp(η) Q = tvq * exp(η) end @dynamics begin Central' = (Q/Vp)*Peripheral - (Q/Vc)*Central -(CL/Vc)*Central Peripheral' = -(Q/Vp)*Peripheral + (Q/Vc)*Central end @derived begin cp = @. Central/Vc """ Observed Concentration (ug/L) """ dv ~ @. Normal(cp, sqrt(cp^2*σ²_prop)) end end
PumasModel Parameters: tvcl, tvvc, tvvp, tvq, Ω, σ²_prop Random effects: η Covariates: Dynamical variables: Central, Peripheral Derived: cp, dv Observed: cp, dv
Parameters provided for simulation.
tv represents the typical value for parameters.
$Cl$ - Clearance (L/kg/hr)
$Vc$ - Volume of Central Compartment (L/kg)
$Vp$ - Volume of Peripheral Compartment (L/kg)
$Q$ - Intercompartmental clearance (L/kg/hr)
$Ω$ - Between Subject Variability
$σ$ - Residual error
param = (tvcl = 0.417793, tvvc = 0.320672, tvvp = 2.12265, tvq = 0.903188, Ω = Diagonal([0.0,0.0,0.0,0.0]), σ²_prop = 0.005)
(tvcl = 0.417793, tvvc = 0.320672, tvvp = 2.12265, tvq = 0.903188, Ω = [0.0 0.0 0.0 0.0; 0.0 0.0 0.0 0.0; 0.0 0.0 0.0 0.0; 0.0 0.0 0.0 0.0], σ²_prop = 0.005)
Single subject receiving three consecutive IV infusion
1st dose: 26.9 mcg/kg over 15min
2nd dose: 139 mcg/kg from 15min to 8hr
3rd dose: 138.95 mcg/kg between 8hr to 24hr
ev1 = DosageRegimen([26.9,139,138.95], time=[0,0.25,8], cmt=1, duration=[0.25,7.85,16]) sub1 = Subject(id=1, events=ev1)
Subject ID: 1 Events: 6
Lets simulate for plasma concentration with the specific observation time points after IV infusion.
Random.seed!(123) sim_sub1 = simobs(pk_39, sub1, param, obstimes=0:0.01:60)
f1, a1, p1 = sim_plot(pk_39, [sim_sub1], observations = :cp, color = :redsblues, linewidth = 4, axis = ( xlabel = "Time (hr)", ylabel = "PK39 Concentrations (μg/L)", xticks = 0:10:60)) f1