title: Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso.
abstract: OBJECTIVE
  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 × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 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.
  
  
  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.
authors.affiliation: Unité de Recherche Paludisme et Maladies Tropicales Négligées, Centre Muraz, Bobo-Dioulasso, Burkina Faso Institut de Recherche en Sciences de la Santé, Unité de Recherche Clinique de Nanoro, Nanoro, Burkina Faso innocentvalea@yahoo.fr.
authors.forename: Innocent
authors.initials: I
authors.lastname: Valea
authors.affiliation: Unité de Recherche Paludisme et Maladies Tropicales Négligées, Centre Muraz, Bobo-Dioulasso, Burkina Faso Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.affiliation: Institut de Recherche en Sciences de la Santé, Unité de Recherche Clinique de Nanoro, Nanoro, Burkina Faso Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest, Bobo-Dioulasso, Burkina Faso.
authors.forename: Maminata
authors.initials: M
authors.lastname: Traore-Coulibaly
authors.affiliation: Unité de Recherche Paludisme et Maladies Tropicales Négligées, Centre Muraz, Bobo-Dioulasso, Burkina Faso.
authors.forename: Laeticia C
authors.initials: LC
authors.lastname: Toe
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Joel
authors.initials: J
authors.lastname: Tarning
authors.affiliation: International Health Unit, University of Antwerp, Antwerp, Belgium.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Van Geertruyden
authors.affiliation: Unit of Epidemiology and Control of Parasitic Diseases, Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium Disease Control and Elimination, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.affiliation: Institutes of Global Health & Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Geraint R
authors.initials: GR
authors.lastname: Davies
authors.affiliation: Molecular and Biochemical Parasitolgy, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077332:Artesunate; D002050:Burkina Faso; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015767:Mefloquine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D000077332:Artesunate; D015767:Mefloquine
keywords: PK; antimalarials; pregnancy