2022
The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial
Whalen ME, Kajubi R, Goodwin J, Orukan F, Colt M, Huang L, Richards K, Wang K, Li F, Mwebaza N, Aweeka FT, Parikh S. The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial. Clinical Infectious Diseases 2022, 76: 443-452. PMID: 36130191, PMCID: PMC9907485, DOI: 10.1093/cid/ciac783.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrineReinfection riskArtemisinin-based combination therapyDay 7 levelsOverall drug exposureHigh transmission settingsYoung childrenAntimalarial exposureUncomplicated malariaExtended regimenRecurrent parasitemiaControlled TrialsPrimary outcomeCombination therapyKaplan-MeierDrug exposureTotal episodesUgandan childrenArtemisinin resistanceLumefantrine concentrationsPharmacodynamic studiesHigh riskPharmacokinetic parametersRecurrence riskDay 7
2018
Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
Kloprogge F, Workman L, Borrmann S, Tékété M, Lefèvre G, Hamed K, Piola P, Ursing J, Kofoed PE, Mårtensson A, Ngasala B, Björkman A, Ashton M, Hietala S, Aweeka F, Parikh S, Mwai L, Davis TME, Karunajeewa H, Salman S, Checchi F, Fogg C, Newton PN, Mayxay M, Deloron P, Faucher JF, Nosten F, Ashley EA, McGready R, van Vugt M, Proux S, Price RN, Karbwang J, Ezzet F, Bakshi R, Stepniewska K, White NJ, Guerin PJ, Barnes KI, Tarning J. Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis. PLOS Medicine 2018, 15: e1002579. PMID: 29894518, PMCID: PMC5997317, DOI: 10.1371/journal.pmed.1002579.Peer-Reviewed Original ResearchConceptsPregnant womenArtemether-lumefantrineCure rateClinical studiesYoung childrenCurrent standard treatment regimenUncomplicated Plasmodium falciparum malariaPharmacokinetic modelAbsorption of lumefantrinePre-treatment parasitaemiaVenous plasma dataAlternative dosing regimensPlasmodium falciparum malariaStandard treatment regimenProspective clinical studyNon-pregnant adultsLow cure ratePopulation pharmacokinetic modelRelevant clinical studiesUseful therapeutic lifeFrequency of dosingConcentration-time dataHigher individual dosesLumefantrine exposureLumefantrine levels
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 modelRethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study
Sambol NC, Tappero JW, Arinaitwe E, Parikh S. Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study. PLOS ONE 2016, 11: e0154623. PMID: 27182702, PMCID: PMC4868321, DOI: 10.1371/journal.pone.0154623.Peer-Reviewed Original ResearchConceptsPopulation pharmacokinetic modelWeekly dosingUncomplicated Plasmodium falciparum malariaSteady-state trough concentrationsPharmacokinetic modelYoung childrenStandard therapeutic dosesYoung Ugandan childrenFirst-line therapyPlasmodium falciparum malariaFuture trial designPeak concentrationPlasma concentration-time profilesPercent of childrenConcentration-time profilesPiperaquine concentrationsMalaria chemopreventionBreakthrough infectionsMonthly administrationTrough concentrationsAcute treatmentFalciparum malariaLoading doseChemopreventive regimensInitial dosing
2013
Pharmacokinetic Predictors for Recurrent Malaria After Dihydroartemisinin-Piperaquine Treatment of Uncomplicated Malaria in Ugandan Infants
Creek DJ, Bigira V, McCormack S, Arinaitwe E, Wanzira H, Kakuru A, Tappero JW, Sandison TG, Lindegardh N, Nosten F, Aweeka FT, Parikh S. Pharmacokinetic Predictors for Recurrent Malaria After Dihydroartemisinin-Piperaquine Treatment of Uncomplicated Malaria in Ugandan Infants. The Journal Of Infectious Diseases 2013, 207: 1646-1654. PMID: 23447696, PMCID: PMC4318925, DOI: 10.1093/infdis/jit078.Peer-Reviewed Original ResearchConceptsPiperaquine concentrationsRecurrent malariaDay 7TMP-SMXDihydroartemisinin-piperaquine treatmentPK/PD studiesTMP-SMX prophylaxisTrimethoprim-sulfamethoxazole prophylaxisTime of presentationPK/PD dataYears of ageYoung childrenPiperaquine exposureUgandan infantsUncomplicated malariaMalaria treatmentPharmacodynamic dataDP useDay 28PD studiesMalariaDay 63Strong associationPQ concentrationProphylaxis
2012
Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria
Tarning J, Zongo I, Somé FA, Rouamba N, Parikh S, Rosenthal PJ, Hanpithakpong W, Jongrak N, Day NP, White NJ, Nosten F, Ouedraogo J, Lindegardh N. Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria. Clinical Pharmacology & Therapeutics 2012, 91: 497-505. PMID: 22258469, PMCID: PMC3736305, DOI: 10.1038/clpt.2011.254.Peer-Reviewed Original ResearchConceptsUncomplicated falciparum malariaFalciparum malariaPopulation pharmacokineticsThree-compartment distribution modelNonlinear mixed-effects modelingRecurrent malaria infectionsTotal piperaquine exposureArtemisinin combination treatmentWeight-normalized dosePlasma concentration-time profilesYoung childrenMixed-effects modelingConcentration-time profilesPiperaquine concentrationsPiperaquine exposureDose regimenMalaria infectionPlasma concentrationsPharmacodynamic propertiesCombination treatmentBody weightPiperaquineSignificant covariatesOlder childrenMalaria