The pharmacokinetics of artemether and lumefantrine in pregnant women with uncomplicated falciparum malaria.
OBJECTIVE
To determine the pharmacokinetic properties of artemether and lumefantrine (AL) in pregnant women with recrudescent uncomplicated multi-drug resistant falciparum malaria.


METHODS
Pregnant women who had recurrence of parasitaemia following 7 days supervised quinine treatment were treated with AL. Serial blood samples were taken over a 7-day period, and pharmacokinetic parameters were estimated. For lumefantrine, these data were compared in a population pharmacokinetic model with data from non-pregnant, mainly male adults with acute malaria.


RESULTS
The pregnant women (five in the second trimester and eight in the third trimester) had lower concentrations of artemether, dihydroartemisinin and lumefantrine, and the elimination of lumefantrine in pregnant women was more rapid than reported previously in non-pregnant adults.


CONCLUSIONS
Pregnancy is associated with reduced plasma concentrations of both artemether and lumefantrine. This is likely to be of therapeutic significance as plasma concentrations of lumefantrine, after elimination of artemether, are an important determinant of cure. Further studies are needed to determine the optimum dose regimen of artemether-lumefantrine in pregnancy.
McGready
Rose
R
Shoklo Malaria Research Unit, P.O. Box 46, Mae Sot, Tak, Thailand.
Stepniewska
Kasia
K
Lindegardh
Niklas
N
Ashley
Elizabeth A
EA
La
Yar
Y
Singhasivanon
Pratap
P
White
Nicholas J
NJ
Nosten
François
F
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D000077549:Artemether; D037621:Artemisinins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D012008:Recurrence; D012074:Remission Induction; D012717:Sesquiterpenes / Q000097:blood; D013607:Tablets; D013785:Thailand
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; D013607:Tablets; C039060:artenimol; D000077549:Artemether; D000078102:Lumefantrine