Simple jQuery Dropdowns
Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/14282
Title: Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda
Authors: Joel Tarning
Frank Kloprogge
Patrice Piola
Mehul Dhorda
Sulaiman Muwanga
Eleanor Turyakira
Nitra Nuengchamnong
François Nosten
Nicholas P J Day
Nicholas J. White
Philippe J. Guerin
Niklas Lindegardh
Nuffield Department of Clinical Medicine
Mahidol University
Epicentre
Epicentre
University of Maryland School of Medicine
University of Science and Technology
Shoklo Malaria Research Unit
Keywords: Immunology and Microbiology;Medicine
Issue Date: 24-Aug-2012
Citation: Malaria Journal. Vol.11, (2012)
Abstract: Background: Malaria 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 approaches. Conclusion: The population pharmacokinetic properties of artemether and dihydroartemisinin, in pregnant women with uncomplicated P. falciparum malaria in Uganda, were described satisfactorily by a simultaneous drug-metabolite model without covariates. Concentrations of artemether and its metabolite dihydroartemisinin were relatively low in pregnancy compared to literature data. However, this should be interpreted with caution considered the limited literature available. Further studies in larger series are urgently needed for this vulnerable group. © 2012 Tarning et al.; licensee BioMed Central Ltd.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84865200031&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/14282
ISSN: 14752875
Appears in Collections:Scopus 2011-2015

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.