PT - JOURNAL ARTICLE AU - Ki Bae Hong AU - Ian Hastings AU - Katherine Kay AU - Eva Maria Hodel TI - Evaluating artesunate-amodiaquine deployment, efficacy and safety: an <em>in silico</em> pharmacological model AID - 10.1101/567008 DP - 2019 Jan 01 TA - bioRxiv PG - 567008 4099 - http://biorxiv.org/content/early/2019/03/14/567008.short 4100 - http://biorxiv.org/content/early/2019/03/14/567008.full AB - Background The World Health Organization currently recommends artesunate-amodiaquine (AS-AQ) as a first-line treatment for uncomplicated falciparum malaria. The clinical efficacy of AS-AQ is very high but its effectiveness in the field varies considerably. This study aimed at comparing the efficacy, effectiveness and safety of AS-AQ fixed dose combination (FDC) and non-fixed formulation (non-FDC) in controlled and real-life settings using a pharmacological model of antimalarial treatment.Methods The effectiveness and safety of different drug formulations in different treatment scenarios were investigated using a pharmacological model of AS-AQ treatment. The model simulated multiple treatment scenarios to assess the effects of age-or weight-based dosing bands in three geographically distinct patient populations, and poor patient adherence.Results The model output was consistent with clinical trials in terms of cure rates, recrudescence rates and the pattern of AQ overdosing with age- and weight-based dosing regimens. AS-AQ treatment has good efficacy and effectiveness in fully adherent patients but monotherapy of AS or AQ lead to treatment failure. The weight-based dosing regimen with FDC was the best option for patients in terms of drug safety and had similar efficacies to the other regimens. Asians were more likely to be overdosed with AQ when using age-based dosing regimens.Conclusions Weight-based dosing is optimal but not always feasible, so age-based dosing regimens are often used as an alternative. The model outputs highlight the importance of optimising these age-based dosing regimens for specific regions, and identify an increased risk of overdosing in young children.ACTartemisinin-based combination therapy AQ amodiaquineAS-AQartesunate-amodiaquine CQ chloroquineCVcoefficient of variationDEAQdesethylamodiaquineDHAdihydroartemisininFDCfixed-dose combinationLoDlimit of microscopic detectionMDAmass drug administrationMQmefloquinePCRpolymerase chain reactionPCTparasite clearance timesPDpharmacodynamicPKpharmacokineticPoCperiods of chemoprophylaxisSPsulphadoxine-pyrimethamineWHOWorld Health OrganizationWWARNWorldwide Antimalarial Resistance Network