Scientific Publications-2010-Malaria

2010

Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial by Smithuis F, Kyaw Kyaw M, Phe O, Win T, Phyo Aung P, Pyay Phyo Oo A, Naing A L, Yee Nyo M, Htun Myint N Z, Imwong M, Ashley E, Lee S J, White N J. The Lancet Infectious Diseases, 2010 September, Vol. 10, Issue 10, Pages 673 - 681.
The Artemisinin-combination therapy (ACT) is recommended as first-line treatment of P. falciparum malaria worldwide, and fixed-dose combinations are preferred by WHO. This study aimed to compare effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate–mefloquine, artesunate–amodiaquine, dihydroartemisinin–piperaquine, artemether–lumefantrine) and a loose tablet combination of artesunate and mefloquine in Burmese adults and children. Artesunate–mefloquine provided the greatest post-treatment suppression of malaria.
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New fixed dose artesunate/mefloquine for treating multidrug resistant Plasmodium falciparum in adults – a comparative phase IIb safety and pharmacokinetic study with standard dose non-fixed artesunate plus mefloquine by Krudsood S, Looareesuwan S, Tangpukdee N, Wilairatama P, Phumratanaprapin W, Leowattana W, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR, Taylor WRJ. AAC, 2010 June, doi:10.1128/AAC.01187-09 
A new fixed dose artesunate (AS)/mefloquine (MQ) was assessed in adults, hospitalized for 28 days, with uncomplicated, drug resistant falciparum malaria.
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Pharmacokinetics and Comparative Bioavailability of Artesunate and Mefloquine Administered Separately or as a Fixed Combination Product to Healthy Volunteers and Patients with Uncomplicated Plasmodium falciparum Malaria by Olliaro P, Ramanathan S, Vaillant M, Reuter S, Evans A, Krudsood S, Looareesuwan S,
Kiechel J-R, Taylor W, and Navaratnam V. Journal of Bioequivalence & Bioavailability, 2010 May, Volume 2(3): 059-066.
The pharmacokinetics of artesunate, dihydroartemisinin, the artesunate metabolite and predominant species and mefloquine were assessed in a single-dose, randomised, crossover design study in healthy volunteers and in a multiple-dose, randomised, parallel group study in patients with uncomplicated falciparum malaria.
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Anti-malarial market and policy surveys in sub-Saharan Africa by Diap G, Amuasi J, Boakye I, Sevcsik A-M, and Pecoul B. Malaria Journal Supplement, BioMed Central 2010 April, 9(1):S1
Following the development by DNDi and the FACT partners of the ASAQ fixed-dose combination, according to WHO recommendations (easy to use, affordable, field adapted and non-patented), and despite the fact that ASAQ fixed-dose combination is registered and available in more than 25 African endemic countries and eligible for Global Fund and other international funding, general access to ACTs for patients is still inadequate.
At the recent meeting (Sept 18, 2009) on public and private market and policy survey: ‘Antimalarial market and policy surveys in sub-Saharan Africa’, a validated methodology for these surveys in two countries (Sierra Leone and Burundi) was discussed. Real-life data were presented in a highly interactive brainstorming session among key stakeholders, in a time when market issues for malaria are at the top of the international agendas.
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Population Pharmacokinetics and Pharmacodynamic considerations of Amodiaquine and Desethylamodiaquine in Kenyan Adults with uncomplicated malaria receiving the Artesunate-Amodiaquine combination therapy by Jullien V, Ogutu B, Juma E, Carn G, Obyono C, and Kiechel J-R. Antimicrobial Agents and Chemotherapy. 2010 April 5. 01496-09.
Amodiaquine (AQ) is an antimalarial drug that was frequently combined with artesunate (AS) for the treatment of uncomplicated malaria due to Plasmodium falciparum and is now available as a fixed dose combination. Despite its widespread use, the simultaneous  pharmacokinetics of AQ and its active metabolite, desethylamodiaquine (DAQ) were not characterized to date in patients. The pharmacokinetics of AQ and DAQ were therefore investigated in 54 adult patients receiving the AS/AQ combination by the use of a population approach. AQ followed a 1-compartment model with first-order absorption and elimination as well as a first-order and irreversible transformation  into DAQ, which in turn followed a 2-compartment model with first-order elimination from its central compartment. Mean AQ apparent clearance and distribution volume were 3410 L/h and 39200 L respectively. Mean terminal elimination half-life of DAQ was 211 h. Bodyweight was found to explain the interindividual variability of the apparent volume of distribution of AQ and the elimination rate constant of DAQ. A new dosage form consisting in a fixed dose combination of AS and AQ was found to have no effect on the pharmacokinetic parameters of AQ and DAQ. All patients achieved parasite clearance within 4 days following the initiation of the treatment, which prevented the investigation of the possible relationship between DAQ exposure and treatment outcome. This study provided the first simultaneous pharmacokinetic model for AQ and DAQ.
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