Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda

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dc.contributor.authorTarning, Joel
dc.contributor.authorKloprogge, Frank
dc.contributor.authorPiola, Patrice
dc.contributor.authorDhorda, Mehul
dc.contributor.authorMuwanga, Sulaiman
dc.contributor.authorTuryakira, Eleanor
dc.contributor.authorNuengchamnong, Nitra
dc.contributor.authorNosten, François
dc.contributor.authorDay, Nicholas P.J.
dc.contributor.authorWhite, Nicholas J.
dc.contributor.authorGuerin, Philippe J.
dc.contributor.authorLindegardh, Niklas
dc.date.accessioned2022-12-14T10:01:04Z
dc.date.available2022-12-14T10:01:04Z
dc.date.issued2012
dc.description.abstractMalaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. Methods: Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies. Results: The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approachesen_US
dc.identifier.citationTarning, J., Kloprogge, F., Piola, P., Dhorda, M., Muwanga, S., Turyakira, E., ... & Lindegardh, N. (2012). Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda. Malaria journal, 11(1), 1-12.en_US
dc.identifier.urihttps://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-11-293
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/6286
dc.language.isoenen_US
dc.publisherMalaria journalen_US
dc.subjectNon-linear mixed effects modelingen_US
dc.subjectPharmacokineticsen_US
dc.subjectArtemetheren_US
dc.subjectDihydroartemisininen_US
dc.titlePopulation pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Ugandaen_US
dc.typeArticleen_US
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