Population Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Uganda

Hdl Handle:
http://hdl.handle.net/10144/311960
Title:
Population Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Uganda
Authors:
Kloprogge, F; Piola, P; Dhorda, M; Muwanga, S; Turyakira, E; Apinan, S; Lindegårdh, N; Nosten, F; Day, N P J; White, N J; Guerin, P J; Tarning, J
Journal:
CPT: Pharmacometrics & Systems Pharmacology
Abstract:
Pregnancy alters the pharmacokinetic properties of many antimalarial compounds. The objective of this study was to evaluate the pharmacokinetic properties of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda after a standard fixed oral artemether-lumefantrine treatment. Dense venous (n = 26) and sparse capillary (n = 90) lumefantrine samples were drawn from pregnant patients. A total of 17 nonpregnant women contributed with dense venous lumefantrine samples. Lumefantrine pharmacokinetics was best described by a flexible absorption model with multiphasic disposition. Pregnancy and body temperature had a significant impact on the pharmacokinetic properties of lumefantrine. Simulations from the final model indicated 27% lower day 7 concentrations in pregnant women compared with nonpregnant women and a decreased median time of 0.92 and 0.42 days above previously defined critical concentration cutoff values (280 and 175 ng/ml, respectively). The standard artemether-lumefantrine dose regimen in P. falciparum malaria may need reevaluation in nonimmune pregnant women.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e83; doi:10.1038/psp.2013.59; advance online publication 13 November 2013.
Affiliation:
1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand [2] Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Issue Date:
2013
URI:
http://hdl.handle.net/10144/311960
DOI:
10.1038/psp.2013.59
PubMed ID:
24226803
Language:
en
ISSN:
2163-8306
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorKloprogge, Fen_GB
dc.contributor.authorPiola, Pen_GB
dc.contributor.authorDhorda, Men_GB
dc.contributor.authorMuwanga, Sen_GB
dc.contributor.authorTuryakira, Een_GB
dc.contributor.authorApinan, Sen_GB
dc.contributor.authorLindegårdh, Nen_GB
dc.contributor.authorNosten, Fen_GB
dc.contributor.authorDay, N P Jen_GB
dc.contributor.authorWhite, N Jen_GB
dc.contributor.authorGuerin, P Jen_GB
dc.contributor.authorTarning, Jen_GB
dc.date.accessioned2014-01-28T16:02:41Z-
dc.date.available2014-01-28T16:02:41Z-
dc.date.issued2013-
dc.identifier.citationPopulation Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Uganda. 2013, 2:e83 CPT Pharmacometrics Syst Pharmacolen_GB
dc.identifier.issn2163-8306-
dc.identifier.pmid24226803-
dc.identifier.doi10.1038/psp.2013.59-
dc.identifier.urihttp://hdl.handle.net/10144/311960-
dc.description.abstractPregnancy alters the pharmacokinetic properties of many antimalarial compounds. The objective of this study was to evaluate the pharmacokinetic properties of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda after a standard fixed oral artemether-lumefantrine treatment. Dense venous (n = 26) and sparse capillary (n = 90) lumefantrine samples were drawn from pregnant patients. A total of 17 nonpregnant women contributed with dense venous lumefantrine samples. Lumefantrine pharmacokinetics was best described by a flexible absorption model with multiphasic disposition. Pregnancy and body temperature had a significant impact on the pharmacokinetic properties of lumefantrine. Simulations from the final model indicated 27% lower day 7 concentrations in pregnant women compared with nonpregnant women and a decreased median time of 0.92 and 0.42 days above previously defined critical concentration cutoff values (280 and 175 ng/ml, respectively). The standard artemether-lumefantrine dose regimen in P. falciparum malaria may need reevaluation in nonimmune pregnant women.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e83; doi:10.1038/psp.2013.59; advance online publication 13 November 2013.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to CPT: Pharmacometrics & Systems Pharmacologyen_GB
dc.subjectMalariaen_GB
dc.subjectMaternal Care/Women's Healthen_GB
dc.titlePopulation Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Ugandaen
dc.contributor.department1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand [2] Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.en_GB
dc.identifier.journalCPT: Pharmacometrics & Systems Pharmacologyen_GB

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