Population pharmacokinetics of mefloquine, piperaquine and artemether-lumefantrine in Cambodian and Tanzanian malaria patients.

Details

Ressource 1Download: BIB_35BEA32B625E.P001.pdf (1001.21 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_35BEA32B625E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population pharmacokinetics of mefloquine, piperaquine and artemether-lumefantrine in Cambodian and Tanzanian malaria patients.
Journal
Malaria Journal
Author(s)
Staehli Hodel E.M., Guidi M., Zanolari B., Mercier T., Duong S., Kabanywanyi A.M., Ariey F., Buclin T., Beck H.P., Decosterd L.A., Olliaro P., Genton B., Csajka C.
ISSN
1475-2875 (Electronic)
ISSN-L
1475-2875
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
12
Pages
235
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
BACKGROUND: Inter-individual variability in plasma concentration-time profiles might contribute to differences in anti-malarial treatment response. This study investigated the pharmacokinetics of three different forms of artemisinin combination therapy (ACT) in Tanzania and Cambodia to quantify and identify potential sources of variability.
METHODS: Drug concentrations were measured in 143 patients in Tanzania (artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine), and in 63 (artesunate, dihydroartemisinin and mefloquine) and 60 (dihydroartemisinin and piperaquine) patients in Cambodia. Inter- and intra-individual variabilities in the pharmacokinetic parameters were assessed and the contribution of demographic and other covariates was quantified using a nonlinear mixed-effects modelling approach (NONMEM®).
RESULTS: A one-compartment model with first-order absorption from the gastrointestinal tract fitted the data for all drugs except piperaquine (two-compartment). Inter-individual variability in concentration exposure was about 40% and 12% for mefloquine. From all the covariates tested, only body weight (for all antimalarials) and concomitant treatment (for artemether only) showed a significant influence on these drugs' pharmacokinetic profiles. Artesunate and dihydroartemisinin could not be studied in the Cambodian patients due to insufficient data-points. Modeled lumefantrine kinetics showed that the target day 7 concentrations may not be achieved in a substantial proportion of patients.
CONCLUSION: The marked variability in the disposition of different forms of ACT remained largely unexplained by the available covariates. Dosing on body weight appears justified. The concomitance of unregulated drug use (residual levels found on admission) and sub-optimal exposure (variability) could generate low plasma levels that contribute to selecting for drug-resistant parasites.
Pubmed
Web of science
Open Access
Yes
Create date
18/08/2013 9:21
Last modification date
20/08/2019 14:23
Usage data