Johan UrsingLars RomboStaffan EksborgLena LarsonAnita BruvollJoel TarningAmabelia RodriguesPoul Erik KofoedDanderyd HospitalMahidol UniversityKarolinska InstitutetNuffield Department of Clinical MedicineUppsala UniversitetKolding SygehusSörmland County CouncilIndepth Network2020-03-262020-03-262020-01-01Antimicrobial Agents and Chemotherapy. Vol.64, No.3 (2020)10986596006648042-s2.0-85079888788https://repository.li.mahidol.ac.th/handle/123456789/53877Copyright © 2020 American Society for Microbiology. All Rights Reserved. Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for 2 more days. Chloroquine concentrations, blood pressure, electrocardiograms (ECGs), parasite density, and adverse events were assessed until day 28. Both dosages were well tolerated, and symptoms resolved by day 3 in parallel with increasing chloroquine concentrations. The median corrected QT (QTc) interval was 12 to 26 ms higher at expected peak concentrations than at day 0 (P < 0.001). Pfcrt 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against P. falciparum with pfcrt 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively. Dosages were well tolerated, and no severe cardiac adverse events occurred. The QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1128/AAC.01846-19