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).

CONCLUSION:

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: Elizabeth A Ashley, Kasia Stepniewska, Niklas Lindegårdh, Rose McGready, Anna Annerberg, Robert Hutagalung, Thida Singtoroj, Gilvary Hla, Al Brockman, Stephane Proux, Jahser Wilahphaingern, Pratap Singhasivanon, Nicholas J White, François Nosten
• Journal: Tropical medicine & international health : TM & IH (Trop Med Int Health) Vol. 12 Issue 2 Pg. 201-8 (Feb 2007) ISSN: 1360-2276 [Print] England
• PMID: 17300626 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Artemether, Lumefantrine Drug Combination
• Artemisinins
• Drug Combinations
• Ethanolamines
• Fluorenes
• Lumefantrine

Topics

• Absorption
• Administration, Oral
• Adolescent
• Adult
• Antimalarials (administration & dosage, blood, pharmacokinetics)
• Area Under Curve
• Artemether, Lumefantrine Drug Combination
• Artemisinins (administration & dosage)
• Drug Administration Schedule
• Drug Combinations
• Drug Resistance, Multiple
• Ethanolamines (administration & dosage, blood, pharmacokinetics)
• Female
• Fluorenes (administration & dosage, blood, pharmacokinetics)
• Humans
• Lumefantrine
• Malaria, Falciparum (blood, drug therapy)
• Male
• Middle Aged
• Treatment Outcome