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Journal Article > Research

Population pharmacokinetics of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda

Kloprogge F, Piola P, Dhorda M, Muwanga S, Turyakira E, Apinan S, Lindegardh N, Nosten F, Day NPJ, White NJ, Guerin PJ, Tarning J
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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.
Countries
Uganda
Subject Area
women's healthmalaria
DOI
10.1038/psp.2013.59
Published Date
13-Nov-2013
PubMed ID
24226803
Languages
English
Journal
CPT: Pharmacometrics and Systems Pharmacology
Volume / Issue / Pages
Volume 2, Issue 11, Pages e83
Issue Date
01-Nov-2013
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