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

Le résumé fourni par la source

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 due to 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. Simulating PK-PD profiles for antimalarial combination therapy, artemether-lumefantrine, for 1000 paediatric patients with Plasmodium falciparum malaria across 16 drug resistance scenarios, we found 28-day cure rates predicted by the deterministic and stochastic models to be equivalent. This confirms the standard deterministic method is an adequate proxy for the underlying stochastic process of parasite death during antimalarial treatment.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.