Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso
Open Access
- 2 June 2014
- journal article
- clinical trial
- Published by Oxford University Press (OUP) in Journal of Antimicrobial Chemotherapy
- Vol. 69 (9), 2499-2507
- https://doi.org/10.1093/jac/dku154
Abstract
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. 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). 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 (656 700 versus 542 400 h × ng/mL; P = 0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735 600 versus 1 499 000 h × ng/mL; P < 0.001) and the total drug exposure to artesunate was 42% higher during pregnancy (89.0 versus 62.9 h × ng/mL; P = 0.039) compared with non-pregnant controls. 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
This publication has 32 references indexed in Scilit:
- Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in UgandaMalaria Journal, 2012
- Pregnancy and Fetal Outcomes After Exposure to Mefloquine in the Pre- and Periconception Period and During PregnancyClinical Infectious Diseases, 2012
- Population Pharmacokinetics of Dihydroartemisinin and Piperaquine in Pregnant and Nonpregnant Women with Uncomplicated MalariaAntimicrobial Agents and Chemotherapy, 2012
- Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effectsBritish Journal of Clinical Pharmacology, 2012
- Pharmacokinetics of Antimalarials in PregnancyClinical Pharmacokinetics, 2011
- Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malariaMalaria Journal, 2011
- Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRCMalaria Journal, 2011
- Population Pharmacokinetics of Lumefantrine in Pregnant Women Treated with Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum MalariaAntimicrobial Agents and Chemotherapy, 2009
- Reducing the burden of malaria in pregnancy by preventive strategiesThe Lancet Infectious Diseases, 2007
- Mefloquine pharmacokinetics in pregnant women with acute falciparum malariaTransactions of the Royal Society of Tropical Medicine and Hygiene, 1994