ModelDrug

Antimalarial drug modelling

There are three different ways of modelling antimalarial drug action in OpenMalaria:

1. A simple success/failure model in which drug treatment either clears all infections in the host (treatSimple option in health system / intervention component) or does nothing. This can be extended to include a prophylactic effect which simply removes all new infections for a configurable number of steps in the future.
2. Clearing infections via above method then using Pre-erythrocytic vaccines to probabilistically prevent reinfection (this allows a slightly more realistic prophylactic effect than the above).
3. Explicit pharmacokinetic and pharmacodynamic (PK/PD) modelling of drugs (treatPKPD option in health system / intervention component), linked to a dynamic model of parasite densities in the course of an infection. The treatment schedules and PK/PD parameterisations can be found in the pharmacology library. The structural PK profile for each drug can be chosen from one of three PK models (described below).

When explicit PK/PD modeling is implemented, the parasite population can be divided into multiple genotypes with different drug resistance phenotypes, for modeling of the spread of drug resistance and its effects.

Structural PK model options

One-compartment PK model

The methodology required to simulate a one-compartment PK model, assuming instantaneous absorption, linear elimination and multiple doses (without lag time) is described in Winter & Hastings (2011).

Absorption-Conversion of a one-compartment PK model (v34 and later)

The methodology required to simulate a one-compartment absorption-conversion PK model was described in Kay & Hastings (2013). It allows for absorption of a drug from the gut at a user-defined rate, into the unconverted parent form in the serum where it is either eliminated (unconverted) or converted into an active metabolite form at a user-defined rate. The active metabolite is then eliminated at a user-defined rate.

Two or three-compartment PK model (v34 and later)

The methodology required to simulate a three-compartment PK model with first-order absorption, linear elimination and multiple doses (without lag time) was described by Bertrand & Mentré (2008) (Equation 1.72). The equations were subsequently edited for inclusion into the OpenMalaria code (edited equations ).

Note a two-compartment PK model can be simulated by setting the inter-compartment clearance between the central and peripheral compartment two to zero.