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Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly observed ideal conditions (n = 136), and the adherence of SMC at an implementation phase in children participating in a case-control study to evaluate SMC effectiveness (n = 869). Amodiaquine and desethylamodiaquine concentration-time profiles were described simultaneously by two-compartment and three-compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65-71% when the first dose of SMC was directly observed and 71-73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case-control children showed complete adherence (all doses taken) in

Original publication

DOI

10.1002/cpt.1707

Type

Journal

Clinical pharmacology and therapeutics

Publication Date

05/2020

Volume

107

Pages

1179 - 1188

Addresses

Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.

Keywords

Humans, Malaria, Amodiaquine, Antimalarials, Chemoprevention, Case-Control Studies, Prospective Studies, Seasons, Models, Biological, Child, Preschool, Infant, Africa, Female, Male, Medication Adherence