Pharmacokinetics of Mefloquine-Artesunate in Pregnant Women With Uncomplicated Plasmodium Falciparum Infection
Status:
Withdrawn
Trial end date:
2010-10-01
Target enrollment:
Participant gender:
Summary
Artemisinin-based combination therapies (ACTs) are now the treatment of choice for malaria in
non-pregnant individuals living in areas with established chloroquine resistance; they have
been shown to be both safe and highly efficacious. There is rapidly increasing experience
with artemisinin derivatives in the 2nd and 3rd trimesters of pregnancy, with over 1,000 well
documented cases with no reported serious adverse effects to mother or fetus (WHO Malaria
Treatment Guidelines, 2006). Many countries in Latin America have abandoned the previous 1st
line regimen of Quinine-Clindamycin for treatment of malaria in pregnancy, a complex and
poorly tolerated regimen with low adherence, in favor of ACTs, despite limited safety and
pharmacokinetic data on the use of these compounds in pregnant women. Lack of pharmacokinetic
data may lead to underdosing of pregnant women, with subsequent reduced efficacy and
increased potential for development of resistance.
One ACT regimen, Artesunate-Mefloquine, has been developed as a fixed-dose combination
(Farmanguinhos Artesunato + Mefloquina), as part of an international collaborative research
effort led by Drugs for Neglected Diseases Initiative (DNDi), and manufactured by
Farmanguinhos, laboratory of the Brazilian Ministry of Health. Initial clinical trials
suggest that it is very well tolerated and efficacious in both pregnant and non-pregnant
individuals. The convenient dosing afforded by a fixed drug combination make this a very
promising candidate for treatment of pregnant women with malaria. Preliminary pharmacokinetic
data from mefloquine monotherapy and prophylaxis suggest that the peak concentration of
mefloquine is lowered in pregnant women. Prior to wide-spread adoption of the
Artesunate-Mefloquine combination, further studies on safety, efficacy, and dose optimization
are imperative. We propose to compare the pharmacokinetics of the fixed combination of
mefloquine-artesunate (MA) for treatment of P.falciparum in 28 pregnant women in the second
and third trimesters to the pharmacokinetics of this regimen in 28 matched non-pregnant
P.falciparum infected women. This will allow us to determine whether the standard adult dose
is sufficient for pregnant women.