title: Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria.
abstract: Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults; however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether-lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicated Plasmodium falciparum malaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.).
authors.affiliation: Institute for Global Health, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, USA.
authors.forename: Myaing M
authors.initials: MM
authors.lastname: Nyunt
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Vy K
authors.initials: VK
authors.lastname: Nguyen
authors.affiliation: Infectious Disease Research Collaboration, Makerere University, Kampala, Uganda.
authors.forename: Richard
authors.initials: R
authors.lastname: Kajubi
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Liusheng
authors.initials: L
authors.lastname: Huang
authors.affiliation: Infectious Disease Research Collaboration, Makerere University, Kampala, Uganda.
authors.forename: Joshua
authors.initials: J
authors.lastname: Ssebuliba
authors.affiliation: Infectious Disease Research Collaboration, Makerere University, Kampala, Uganda.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kiconco
authors.affiliation: Infectious Disease Research Collaboration, Makerere University, Kampala, Uganda.
authors.forename: Moses W
authors.initials: MW
authors.lastname: Mwima
authors.affiliation: Infectious Disease Research Collaboration, Makerere University, Kampala, Uganda.
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.affiliation: Yale School of Public Health, New Haven, Connecticut, USA sunil.parikh@yale.edu mwebno@yahoo.com.
authors.forename: Sunil
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Infectious Disease Research Collaboration, Makerere University, Kampala, Uganda sunil.parikh@yale.edu mwebno@yahoo.com.
authors.forename: Norah
authors.initials: N
authors.lastname: Mwebaza
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008875:Middle Aged; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome; D014454:Uganda; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; C039060:artenimol; D000077549:Artemether; D000078102:Lumefantrine