| Innocent Valea, Halidou Tinto, Maminata Traore-Coulibaly, Laeticia C Toe, Niklas Lindegardh, Joel Tarning, Jean-Pierre Van Geertruyden, Umberto D’Alessandro, Geraint R Davies, Stephen A Ward Pharmacokinetics of co-formulated mefloquine and artesunate in
pregnant and non-pregnant women with uncomplicated Plasmodium
falciparum infection in Burkina Faso (Journal Article) In: J. Antimicrob. Chemother., vol. 69, no. 9, pp. 2499–2507, 2014. @article{Valea2014-gm,
title = {Pharmacokinetics of co-formulated mefloquine and artesunate in
pregnant and non-pregnant women with uncomplicated Plasmodium
falciparum infection in Burkina Faso},
author = {Innocent Valea and Halidou Tinto and Maminata Traore-Coulibaly and Laeticia C Toe and Niklas Lindegardh and Joel Tarning and Jean-Pierre Van Geertruyden and Umberto D'Alessandro and Geraint R Davies and Stephen A Ward},
year = {2014},
date = {2014-09-01},
journal = {J. Antimicrob. Chemother.},
volume = {69},
number = {9},
pages = {2499--2507},
publisher = {Oxford University Press (OUP)},
abstract = {OBJECTIVES: Mefloquine/artesunate has recently been developed as
a fixed-dose combination, providing a promising
rescue/alternative treatment for malaria during pregnancy.
However, limited data are available on the effect of pregnancy
on its pharmacokinetic properties. This study was conducted to
assess the pharmacokinetic properties of
mefloquine/carboxymefloquine and artesunate/dihydroartemisinin
in pregnant and non-pregnant women with uncomplicated malaria.
METHODS: Twenty-four women in their second and third trimesters
of pregnancy and 24 paired non-pregnant women were enrolled. All
patients were treated for uncomplicated Plasmodium falciparum
malaria with a standard fixed-dose combination of oral
mefloquine and artesunate one daily over 3 days. Frequent blood
samples were collected before treatment and at scheduled times
post-dose for the drug measurements and pharmacokinetic
analyses. The study was registered at www.clinicaltrials.gov
(identifier: NCT00701961). RESULTS: The total median exposure to
mefloquine and dihydroartemisinin was not significantly
different between the pregnant and non-pregnant women (P\>0.05).
There was a trend of higher exposure to mefloquine in the
pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h $times$ ng/mL; P=0.059).
However, the total exposure to carboxymefloquine was 49% lower
during pregnancy (735600 versus 1499000 h $times$ ng/mL;
P\<0.001) and the total drug exposure to artesunate was 42%
higher during pregnancy (89.0 versus 62.9 h $times$ ng/mL; P=0.039) compared with non-pregnant controls. CONCLUSIONS: The
plasma levels of mefloquine and dihydroartemisinin appeared to
be similar in both pregnant and non-pregnant women, but there
were significant differences in carboxymefloquine and artesunate
exposure. The data presented here do not warrant a dose
adjustment in pregnant patients, but an extensive analysis of
the data could provide a better understanding of these findings.},
keywords = {PK; antimalarials; pregnancy},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: Mefloquine/artesunate has recently been developed as
a fixed-dose combination, providing a promising
rescue/alternative treatment for malaria during pregnancy.
However, limited data are available on the effect of pregnancy
on its pharmacokinetic properties. This study was conducted to
assess the pharmacokinetic properties of
mefloquine/carboxymefloquine and artesunate/dihydroartemisinin
in pregnant and non-pregnant women with uncomplicated malaria.
METHODS: Twenty-four women in their second and third trimesters
of pregnancy and 24 paired non-pregnant women were enrolled. All
patients were treated for uncomplicated Plasmodium falciparum
malaria with a standard fixed-dose combination of oral
mefloquine and artesunate one daily over 3 days. Frequent blood
samples were collected before treatment and at scheduled times
post-dose for the drug measurements and pharmacokinetic
analyses. The study was registered at www.clinicaltrials.gov
(identifier: NCT00701961). RESULTS: The total median exposure to
mefloquine and dihydroartemisinin was not significantly
different between the pregnant and non-pregnant women (P>0.05).
There was a trend of higher exposure to mefloquine in the
pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h $times$ ng/mL; P=0.059).
However, the total exposure to carboxymefloquine was 49% lower
during pregnancy (735600 versus 1499000 h $times$ ng/mL;
P<0.001) and the total drug exposure to artesunate was 42%
higher during pregnancy (89.0 versus 62.9 h $times$ ng/mL; P=0.039) compared with non-pregnant controls. CONCLUSIONS: The
plasma levels of mefloquine and dihydroartemisinin appeared to
be similar in both pregnant and non-pregnant women, but there
were significant differences in carboxymefloquine and artesunate
exposure. The data presented here do not warrant a dose
adjustment in pregnant patients, but an extensive analysis of
the data could provide a better understanding of these findings. |
