title: Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria.
abstract: BACKGROUND
  Adherence to antimalarial drug regimens is improved by simple dosing. If the fixed antimalarial drug combination artemether-lumefantrine (AL) could be given once daily, this should improve adherence and thus effectiveness and lower the risk of selecting for resistance.
  
  
  METHODS
  In an open randomized study, 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days. The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves (AUC). Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles.
  
  
  RESULTS
  Lumefantrine pharmacokinetic profiles were obtained for 36 patients. The AUC((0-->infinity)) of the once-daily regimen was 30% lower than that in the conventional regimen (P = 0.011) with a median (range) value of 306 (114-5781) microg/ml h, compared with 432 (308-992) microg/ml h. There was no significant difference in the peak plasma concentrations reached. PCR-adjusted cure rate estimates at day 42 of follow-up were 94% (95% CI: 84-100) in the six-dose arm and 85% (70-100) in the three-dose arm (P = 0.3).
  
  
  CONCLUSIONS
  Artemether-lumefantrine efficacy is reduced by once-daily dosing, because absorption of lumefantrine is dose limited. At currently recommended doses, this antimalarial should be given twice daily in a 3-day regimen, with food containing fat.
authors.affiliation: Shoklo Malaria Research Unit, Mae Sot, Thailand. smru@tropmedres.ac
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegårdh
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.forename: Anna
authors.initials: A
authors.lastname: Annerberg
authors.forename: Robert
authors.initials: R
authors.lastname: Hutagalung
authors.forename: Thida
authors.initials: T
authors.lastname: Singtoroj
authors.forename: Gilvary
authors.initials: G
authors.lastname: Hla
authors.forename: Al
authors.initials: A
authors.lastname: Brockman
authors.forename: Stephane
authors.initials: S
authors.lastname: Proux
authors.forename: Jahser
authors.initials: J
authors.lastname: Wilahphaingern
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: François
authors.initials: F
authors.lastname: Nosten
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D004983:Ethanolamines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine