Quantification of cure for pharmacodynamic models of antimalarial drugs: Deterministic versus stochastic approaches

Abstract

In silico pharmacokinetic–pharmacodynamic (PK–PD) models are used to inform dose optimisation in antimalarial drug development. Here the PK–PD models capture the change in parasite count over time because of exposure to antimalarial drug(s). For current deterministic PD models, simulated parasite numbers decline proportionally during treatment asymptotically approaching zero, requiring a cure threshold to be selected. We implemented an alternative stochastic model, where parasite-time profiles were simulated using a binomial function with an hourly parasite survival probability. This probabilistic model enables a time of exact cure to be calculated, when zero parasites remain. The 28-day cur..