Day-7 lumefantrine exposure following artemether-lumefantrine treatment under routine outpatient conditions in a high-transmission Mozambican setting.

Artemether-lumefantrine remains the most widely used first-line treatment for uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa, yet pharmacokinetic data describing lumefantrine exposure under routine programmatic conditions remain limited in many endemic settings. This study evaluated day-7 lumefantrine concentrations among adults treated with artemether-lumefantrine for uncomplicated malaria under routine outpatient conditions in Mozambique and assessed the proportion of patients achieving pharmacokinetic thresholds associated with adequate therapeutic exposure. A prospective cohort study was conducted in Quelimane, Zambezia Province, Mozambique, between January and May 2024. Patients with microscopy-confirmed uncomplicated P. falciparum malaria received artemether-lumefantrine according to national treatment guidelines. Day-7 lumefantrine concentrations were quantified from dried blood spots using validated high-performance liquid chromatography. Concentrations ≥280 ng/mL and ≥500 ng/mL were used to characterize adequate exposure, while concentrations <200 ng/mL were considered indicative of underexposure. Multivariable logistic regression was performed to explore demographic predictors of lumefantrine exposure. Sixty-three adults were included in the analysis. The median day-7 lumefantrine concentration was 1002 ng/mL (IQR 544-1220.5), ranging from 60 to 2497 ng/mL. Most participants achieved concentrations ≥280 ng/mL (93.7%), and 77.8% exceeded the higher threshold of 500 ng/mL. Three individuals remained parasitemic on day 7 despite lumefantrine concentrations above 500 ng/mL. Multivariable analysis including age, sex, and body weight did not identify independent predictors of lumefantrine exposure at any evaluated threshold. Overall, lumefantrine exposure under routine outpatient conditions was generally adequate, although substantial interindividual variability was observed. These findings support the continued effectiveness of artemether-lumefantrine in this setting and highlight the potential value of pharmacokinetic monitoring as a complementary component of antimalarial therapeutic surveillance.