Simulate repeated dosing

This guide shows how to schedule repeated doses with TimeSwitcher and simulate two dosing series separated by a treatment break.

Use one switcher for each series. At every scheduled time, an event adds a dose to the drug already present in the compartment.

Before you start, follow the Quick start to install Julia, HetaSimulator, and Plots.

Create this directory with two files:

repeated-dosing/
├── index.heta  # elimination model and dosing events
└── run.jl      # simulation and plot

Define the dosing schedule

Create index.heta with the complete content below:

/* A simple one-compartment model with first-order drug elimination. */
central @Compartment .= 1;
drug @Species { compartment: central, output: true } .= 0;
elimination @Reaction { actors: drug => } := k_elim * drug * central;
k_elim @Const = 1e-2;

/*
  First series: four doses of 10 at times 144, 168, 192, and 216.
  Add dose / volume to the current concentration at each event.
*/
series1 @TimeSwitcher { start: 144, period: 24, stop: 216 };
dose1 @Const = 10;
drug [series1]= drug + dose1 / central;

/* Second series: four doses of 20 after a treatment break. */
series2 @TimeSwitcher { start: 384, period: 24, stop: 456 };
dose2 @Const = 20;
drug [series2]= drug + dose2 / central;

start is the first dosing time, period is the interval between doses, and stop limits the series. Here, stop falls on a scheduled time, so that last dose is included:

Series	Dosing times	Dose
series1	144, 168, 192, 216	10
series2	384, 408, 432, 456	20

The assignment drug [series1]= ... runs whenever series1 fires. Because drug is a concentration and dose1 is an amount, divide the dose by the compartment volume. Keep drug + on the right-hand side to add the dose rather than replace the current concentration.

This illustrative model uses arbitrary consistent units. Between doses, the drug is removed by the elimination reaction; no doses occur during the break between the two series.

Simulate the model

Create run.jl:

using HetaSimulator, Plots

platform = load_platform(".")
model = models(platform)[:nameless]
Scenario(model, (0., 600.)) |> sim |> plot

Run the file in Julia. The simulation covers both series and the decline after the last dose. output: true selects the drug concentration for plotting.

Each dose produces an immediate concentration increase, followed by elimination. Repeated doses accumulate, and the second series uses twice the dose of the first.

Change the regimen

Change start, period, and stop to move or extend a series, and change dose1 or dose2 to adjust its dose. Add another TimeSwitcher and event assignment for a third series. Then reload the platform and rerun the simulation.