Marie A. OnyambokoRichard M. HoglundSue J. LeeCharlie KabediDaddy KayembeBenjamin B. BadjangaGareth D.H. TurnerNikky V. JacksonJoel TarningRose McGreadyFrancois NostenNicholas J. WhiteNicholas P.J. DayCaterina FanelloUniversite de KinshasaNHS Foundation TrustUniversity of OxfordMahidol UniversityNuffield Department of Clinical Medicine2020-03-262020-03-262020-01-01Antimicrobial Agents and Chemotherapy. Vol.64, No.3 (2020)10986596006648042-s2.0-85080033317https://repository.li.mahidol.ac.th/handle/20.500.14594/53874Copyright © 2020 Onyamboko et al. Artemether-lumefantrine antimalarial efficacy in pregnancy could be compromised by reduced drug exposure. Population-based simulations suggested that therapeutic efficacy would be improved if the treatment duration was increased. We assessed the efficacy, tolerability, and pharmacokinetics of an extended 5-day regimen of artemether-lumefantrine compared to the standard 3-day treatment in 48 pregnant women and 48 nonpregnant women with uncomplicated falciparum malaria in an open-label, randomized clinical trial. Babies were assessed at birth and 1, 3, 6, and 12 months. Nonlinear mixed-effects modeling was used to characterize the plasma concentration-time profiles of artemether and lumefantrine and their metabolites. Both regimens were highly efficacious (100% PCR-corrected cure rates) and well tolerated. Babies followed up to 1 year had normal development. Parasite clearance half-lives were longer in pregnant women (median [range], 3.30 h [1.39 to 7.83 h]) than in nonpregnant women (2.43 h [1.05 to 6.00 h]) (P=0.005). Pregnant women had lower exposures to artemether and dihydroartemisinin than nonpregnant women, resulting in 1.2% decreased exposure for each additional week of gestational age. By term, these exposures were reduced by 48% compared to nonpregnant patients. The overall exposure to lumefantrine was improved with the extended regimen, with no significant differences in exposures to lumefantrine or desbutyl-lumefantrine between pregnant and nonpregnant women. The extended artemether-lumefantrine regimen was well tolerated and safe and increased the overall antimalarial drug exposure and so could be a promising treatment option in pregnancy in areas with lower rates of malaria transmission and/or emerging drug resistance.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1128/AAC.01140-19