2022
Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda
Kay K, Goodwin J, Ehrlich H, Ou J, Freeman T, Wang K, Li F, Wade M, French J, Huang L, Aweeka F, Mwebaza N, Kajubi R, Riggs M, Ruiz‐Garcia A, Parikh S. Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda. Clinical Pharmacology & Therapeutics 2022, 113: 660-669. PMID: 36260349, PMCID: PMC9981240, DOI: 10.1002/cpt.2768.Peer-Reviewed Original ResearchConceptsLopinavir-ritonavirLumefantrine concentrationsSensitive parasitesRecurrence riskPopulation PK/PD modelArtemether-lumefantrine treatmentTrimethoprim-sulfamethoxazole prophylaxisPK/PD modelPopulation PK modelFirst-order absorptionHigh transmission regionsAntiretroviral regimensLumefantrine exposureLumefantrine susceptibilityPfcrt K76Pfmdr1 N86Suboptimal dosingArtemether-lumefantrineTwo-compartment modelHIV statusRecurrent infectionsCombination therapyDrug exposurePrimary treatmentArtemisinin resistance
2016
Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
Tchaparian E, Sambol NC, Arinaitwe E, McCormack SA, Bigira V, Wanzira H, Muhindo M, Creek DJ, Sukumar N, Blessborn D, Tappero JW, Kakuru A, Bergqvist Y, Aweeka FT, Parikh S. Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria. The Journal Of Infectious Diseases 2016, 214: 1243-1251. PMID: 27471317, PMCID: PMC5034953, DOI: 10.1093/infdis/jiw338.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrineRecurrent parasitemiaLumefantrine exposurePopulation pharmacokineticsUgandan childrenYoung Ugandan childrenPlasmodium falciparum malariaDay 7 concentrationsAge 6 monthsFirst-order absorptionWhole blood concentrationsYoung childrenUncomplicated malariaFalciparum malariaBlood concentrationsTreatment outcomesLumefantrine concentrationsSignificant positive correlationParasitemiaOlder childrenPharmacokineticsLumefantrineMalariaExposure levelsOpen model
2015
Population Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin‐Piperaquine for Uncomplicated Malaria
Sambol N, Yan L, Creek D, McCormack S, Arinaitwe E, Bigira V, Wanzira H, Kakuru A, Tappero J, Lindegardh N, Tarning J, Nosten F, Aweeka F, Parikh S. Population Pharmacokinetics of Piperaquine in Young Ugandan Children Treated With Dihydroartemisinin‐Piperaquine for Uncomplicated Malaria. Clinical Pharmacology & Therapeutics 2015, 98: 87-95. PMID: 25732044, PMCID: PMC5088713, DOI: 10.1002/cpt.104.Peer-Reviewed Original ResearchConceptsUncomplicated malariaPopulation pharmacokineticsYoung Ugandan childrenWeight-based dosingChildren 6 monthsAge-specific guidelinesClearance/bioavailabilityFirst-order absorptionDihydroartemisinin-PiperaquinePiperaquine exposureMalaria episodesProspective trialOral dosesUgandan childrenPlasma concentrationsThree-compartment modelDay 7High dosesAge groupsEarly childhoodPiperaquineDosingPharmacokineticsMalariaPhysiological changes