Publication: Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda.
Accepted Date
2012-08-15
Issued Date
2012-08-22
Copyright Date
2012
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Tarning J, Kloprogge F, Piola P, Dhorda M, Muwanga S, Turyakira E, et al. Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda. Malar J. 2012 Aug 22;11:293.
Suggested Citation
Tarning, Joel, Kloprogge, Frank, Piola, Patrice, Dhorda, Mehul, Muwanga, Sulaiman, Turyakira, Eleanor, Nitra Nuengchamnong, นิทรา เนื่องจำนงค์, Nosten, François, Day, Nicholas P.J., White, Nicholas J., Guerin, Philippe J., Lindegardh, Niklas Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda.. Tarning J, Kloprogge F, Piola P, Dhorda M, Muwanga S, Turyakira E, et al. Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda. Malar J. 2012 Aug 22;11:293.. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/714
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Title
Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda.
Corresponding Author(s)
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.