Structural model - One compartment turnover model

Route of administration - Intravenous infusion

Dosage Regimen - 400 mg dose given as 19 minute constant intravenous infusion

Number of Subjects - 1 ( Healthy Volunteer )

In this tutorial, you will learn how to build One compartment turnover model with constant intravenous infusion and simulate the model for one single subject and single dosage regimen.

call the "necessary" libraries to get started.

using Pumas using CSV using StatsPlots using Plots using Random

In this one compartment model, we administer dose on central compartment.

pk_49 = @model begin @param begin tvcl ∈ RealDomain(lower=0) tvvc ∈ RealDomain(lower=0) tvsynthesis ∈ RealDomain(lower=0) Ω ∈ PDiagDomain(3) σ_add ∈ RealDomain(lower=0) end @random begin η ~ MvNormal(Ω) end @pre begin CL = tvcl * exp(η[1]) Vc = tvvc * exp(η[2]) Synthesis = tvsynthesis * exp(η[3]) end @init begin Central = Synthesis/(CL/Vc) #we add Vc here because we want it in "amount". not conc. end @dynamics begin Central' = Synthesis - (CL/Vc)*Central end @derived begin cp = @. Central/Vc dv ~ @. Normal(cp, σ_add) end end

PumasModel Parameters: tvcl, tvvc, tvsynthesis, Ω, σ_add Random effects: η Covariates: Dynamical variables: Central Derived: cp, dv Observed: cp, dv

The parameters are as given below. `tv`

represents the typical value for parameters.

Cl - Clearance (L/hr)

Vc - Volume of Central Compartment (L)

Synthesis - Synthesis of endogenous coagulation Factor II (mg/hr)

Ω - Between Subject Variability

σ - Residual error

param = ( tvcl = 0.14204, tvvc = 3.59259, tvsynthesis = 16.2272, Ω = Diagonal([0.0,0.0,0.0]), σ_add = 2.96)

(tvcl = 0.14204, tvvc = 3.59259, tvsynthesis = 16.2272, Ω = [0.0 0.0 0.0; 0 .0 0.0 0.0; 0.0 0.0 0.0], σ_add = 2.96)

A single dose of 400 mg is given as an IV-Infusion over a period of 19 minutes in a healthy individual.

ev1 = DosageRegimen(400, cmt=1, duration=0.3166) sub1 = Subject(id=1, events=ev1)

Subject ID: 1 Events: 2

Lets simulate for plasma concentration with the specific observation time points after Intravenous administration.

Random.seed!(123) sim_sub1 = simobs(pk_49, sub1, param, obstimes=0.00:0.01:160) df1 = DataFrame(sim_sub1)

df1_dv = filter(x -> x.time in [0.01,0.05,0.08,0.16,0.25,0.5,1,2,3,4,5,6,7,8,9,12,15,18,24,32,48,72,96,144], df1) @df df1 plot(:time, :cp, title="Observed mean factor II Conc vs Time", label= "Pred - Conc", xlabel="Time (hr)", ylabel="Concentration (ug/L)", linewidth=3, xticks=[0,20,40,60,80,100,120,140,160], xlims=(-0.5,160), color=[:blue], yticks=[0,80,100,120,140,160,180,200,220,240,260,280,300], ylims=(80,240)) @df df1_dv scatter!(:time, :dv, label="Obs - Conc", color=[:red])