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 drugs structural PK profile can be chosen from one of three PK models (described below).

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).

Three-compartment PK model (versions 34 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).

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

Absorption conversion PK model (versions 34 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.