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
2020
Efavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women.
Hughes E, Mwebaza N, Huang L, Kajubi R, Nguyen V, Nyunt MM, Orukan F, Mwima MW, Parikh S, Aweeka F. Efavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2020, 83: 140-147. PMID: 31929402, PMCID: PMC7061940, DOI: 10.1097/qai.0000000000002237.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlkynesAnti-HIV AgentsAntimalarialsAnti-Retroviral AgentsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsBenzoxazinesCyclopropanesDrug CombinationsDrug InteractionsFemaleHIV InfectionsHumansLumefantrineMalariaMalaria, FalciparumPregnancyProspective StudiesUgandaYoung AdultConceptsEfavirenz-based antiretroviral therapyImpact of efavirenzPregnant womenArtemether-lumefantrineMalaria treatmentAntiretroviral therapyEfavirenz therapyIntensive PK evaluationPK exposure parametersPlasmodium falciparum malariaEffect of efavirenzActive metabolite dihydroartemisininAntimalarial exposureClinical responseFalciparum malariaPregnant HIVTreatment regimenNonsignificant reductionClinical pharmacokinetic studiesPK evaluationDrug interactionsLumefantrine concentrationsHIVTreatment durationPK samples
2016
Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children
Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children. Clinical Infectious Diseases 2016, 63: 414-422. PMID: 27143666, PMCID: PMC4946019, DOI: 10.1093/cid/ciw291.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrine treatmentLPV/rRecurrent malariaLumefantrine exposureDrug exposureCritical drug-drug interactionsFirst-line antiretroviral therapy regimensArtemisinin-based combination therapyLopinavir/ritonavirAntiretroviral therapy regimensPlasmodium falciparum malariaHuman immunodeficiency virusDay 7 concentrationsMalaria-endemic regionsDrug-drug interactionsAntimalarial exposureAntimalarial componentPharmacokinetic samplingArtemether-lumefantrineFalciparum malariaClinical outcomesDosing regimensTherapy regimensImmunodeficiency virusCombination therapy
2015
Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria
Nyunt MM, Nguyen VK, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Mwima MW, Achan J, Aweeka F, Parikh S, Mwebaza N. Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria. Antimicrobial Agents And Chemotherapy 2015, 60: 1274-1282. PMID: 26666942, PMCID: PMC4775973, DOI: 10.1128/aac.01605-15.Peer-Reviewed Original ResearchConceptsNonpregnant adultsPregnant womenArtemether-lumefantrineFalciparum malariaUncomplicated Plasmodium falciparum malariaPharmacokinetics of artemetherPregnant Ugandan womenSix-dose regimenFirst-line regimenUncomplicated falciparum malariaPlasmodium falciparum malariaHigh transmission settingsUncomplicated malariaClinical responsePharmacokinetic exposureTerminal eliminationClinical outcomesThird trimesterTreatment responseAntimalarial efficacyProphylactic periodUgandan womenPharmacokineticsDrug resistanceOverall pharmacokineticsPopulation 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 ResearchMeSH KeywordsAntimalarialsArtemisininsChild, PreschoolDrug Therapy, CombinationHumansInfantMalariaProspective StudiesQuinolinesUgandaConceptsUncomplicated 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
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