Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.
Taylor, W R J
Guthmann, J P
AffiliationEpicentre, Paris, France. firstname.lastname@example.org
MetadataShow full item record
AbstractBACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination.
- Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria.
- Authors: Ashley EA, Stepniewska K, Lindegårdh N, McGready R, Annerberg A, Hutagalung R, Singtoroj T, Hla G, Brockman A, Proux S, Wilahphaingern J, Singhasivanon P, White NJ, Nosten F
- Issue date: 2007 Feb
- A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.
- Authors: Lefèvre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I, Mull R, Bakshi R
- Issue date: 2001 May-Jun
- A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire.
- Authors: Toure OA, Penali LK, Yapi JD, Ako BA, Toure W, Djerea K, Gomez GO, Makaila O
- Issue date: 2009 Jul 3
- Adherence to a six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Uganda.
- Authors: Fogg C, Bajunirwe F, Piola P, Biraro S, Checchi F, Kiguli J, Namiiro P, Musabe J, Kyomugisha A, Guthmann JP
- Issue date: 2004 Nov
- Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India.
- Authors: Valecha N, Srivastava P, Mohanty SS, Mittra P, Sharma SK, Tyagi PK, Pradhan K, Dev V, Singh R, Dash AP, Sharma YD
- Issue date: 2009 May 19