2009
Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda
Mwesigwa J, Parikh S, McGee B, German P, Drysdale T, Kalyango JN, Clark TD, Dorsey G, Lindegardh N, Annerberg A, Rosenthal PJ, Kamya MR, Aweeka F. Pharmacokinetics of Artemether-Lumefantrine and Artesunate-Amodiaquine in Children in Kampala, Uganda. Antimicrobial Agents And Chemotherapy 2009, 54: 52-59. PMID: 19841149, PMCID: PMC2798532, DOI: 10.1128/aac.00679-09.Peer-Reviewed Original ResearchConceptsArtemisinin-based combination therapyUncomplicated malariaActive metaboliteConcentration-time curveWorld Health OrganizationACT regimensArtesunate-AmodiaquineLast doseArtemether-lumefantrineLevel of exposureDrug regimensVenous samplingCombination therapyUgandan childrenPK parametersPharmacokinetic dataArtemisinin derivativesPK resultsOptimum dosingRegimensLumefantrineHealth OrganizationAdultsChildrenDesethylamodiaquine
2007
Amodiaquine Metabolism is Impaired by Common Polymorphisms in CYP2C8: Implications for Malaria Treatment in Africa
Parikh S, Ouedraogo J, Goldstein JA, Rosenthal PJ, Kroetz DL. Amodiaquine Metabolism is Impaired by Common Polymorphisms in CYP2C8: Implications for Malaria Treatment in Africa. Clinical Pharmacology & Therapeutics 2007, 82: 197-203. PMID: 17361129, DOI: 10.1038/sj.clpt.6100122.Peer-Reviewed Original ResearchMeSH KeywordsAlkynesAmodiaquineAntimalarialsAryl Hydrocarbon HydroxylasesBenzoxazinesBurkina FasoChromatography, High Pressure LiquidCyclopropanesCytochrome P-450 CYP2C8Dose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsGenotypeHIV Protease InhibitorsHumansLopinavirMalaria, FalciparumModels, BiologicalPolymorphism, GeneticPyridinesPyrimidinonesPyronesReverse Transcriptase InhibitorsSaquinavirSpectrophotometry, UltravioletSulfonamidesTreatment OutcomeTrimethoprimConceptsAntimalarial drug amodiaquineMalaria-infected patientsAntiretroviral drug efavirenzImportant clinical implicationsAmodiaquine metabolismCYP2C8 genotypeMalaria treatmentN-desethylamodiaquineCYP2C8 variantsCYP2C8 activityCYP2C8 inhibitorsDrug interactionsDefective metabolismClinical implicationsCYP2C8Common polymorphismsDrug efavirenzMetabolismRelevant concentrationsDrugsEfficacyPrimary metabolitesAllele frequenciesToxicitySample size