Scientific Publications-2009-Malaria

2009

Efficacy of artesunate-amodiaquine for treating uncomplicated P. falciparum malaria in Sub-Saharan Africa: a multi-centre analysis by Zwang J, Olliaro P, Barennes H, Bonnet M, Brasseur P, Bukirwa H, Cohuet S, D'Alessandro U, Djimde A, Martensson A, Yeka A, Karema C, Guthmann J-P, Hamour S, Ndiaye J-L, Rwagacondo C, Sagara I, Same-Ekobo A, Sirima S, van den Broek I, Taylor W, Dorsey G, Randrianarivelojosia M. Malaria Journal 2009 Aug 23; 8:203.
This multi-centre analysis led by Julien Zwang at the Shoklo Malaria Research Unit addresses the efficacy of artesunate-amodiaquine, a very important candidate for the treatment of uncomplicated malaria globally. The analysis of patient-level data examining the efficacy of AS&AQ compared with local standard therapy, makes a strong case for the use of AS&AQ in all transmission settings. The analysis, sponsored by DNDi, has pooled data from 26 drug studies in a majority of paediatric malaria cases in sub-Saharan Africa identified through a systematic search and has focused on efficacy as safety will be reported separately. While not without limitations, this analysis contributes to the evidence base as to the proper use of ACTs, particularly the AS&AQ combination, and has provided results consistent with the recently published Cochrane systematic review and meta-analysis on ACTs (including AS&AQ.)
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Population pharmacokinetics of artesunate and amodiaquine in African children by Stepniewska K, Taylor W, Sirima S.B, Ouedraogo E.B, Ouedraogo A, Gansane A, Simpson J.A, Morgan C.C, White N.J, Kiechel J-R. Malaria Journal 2009 Aug 20, 8:200.
Pharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this prospective population pharmacokinetic study of AS and AQ was to evaluate the PK properties of “ASAQ”, a newly developed and registered fixed dose combination (FDC) of AS and AQ in African children. Conducted in 70 children aged six months to five years, the study utilized population PK models for dihydroartemisinin (DHA) and desethylamodiaquine (DeAq), the principal pharmacologically active metabolites of AS and AQ, respectively, and total artemisinin anti-malarial activity. Relative bioavailability between products was compared by estimating the ratios (and 95% CI) between the areas under the plasma concentration-time curves (AUC). The bioavailability of the co-formulated AS-AQ FDC was similar to that of the separate tablets for desethylamodiaquine, DHA and the total anti-malarial activity. These data support the use this new AS-AQ FDC in children with acute uncomplicated falciparum malaria.
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Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria by Ndiaye J-L, Randrianarivelojosia M, Sagara I, Brasseur P, Ndiaye I, Faye B, Randrianasolo L, Ratsimbasoa, Forlemu D, Moor V A, Traore A, Dicko Y, Dara N, Lameyre V, Diallo M, Djimde A, Same-Ekobo A, Gaye O. Malaria Journal 2009 Jun 8; 8:125.
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Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers by Navaratnam V, Ramanathan S, Wahab MSA, Hua GS, Mansor SM, Kiechel JR, Vaillant M, Taylor WRJ, Olliaro P. Eur J Clin Pharmacol 2009 Apr 30.
Due to limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria, this study examined the bioavailability and tolerability of a fixed and loose combination of artesunate + amodiaquine with a 2×2 cross-over design in 24 healthy volunteers. The authours concluded that both combinations were well tolerated and had comparable pharmacokinetic profiles, and that differences are unlikely to be clinically relevant.
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The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum by Sirima SB, Tiono AB, Gansané A, Diarra A, Ouédraogo A, Konaté AT, Kiechel JR, Morgan CC, Olliaro PL, Taylor WRJ. Malaria Journal 2009 Mar 16; 8:48.
A new fixed-dose combination of artesunate (AS) and amodiaquine (AQ) was tested for the first time in a field study comparing its efficacy and safety with the corresponding non-fixed combination. Conducted in Burkina Faso children suffering from P. falciparum malaria, the study incorporated a new, simplified, age-based dosing regimen with the fixed-dose combination. The results show that the AS and AQ, one of  the artemisinin-based combinations (ACT) recommended by the WHO, is highly efficacious and well tolerated.
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Validation of high performance liquid chromatography-electrochemical detection methods with simultaneous extraction procedure for the determination of artesunate, dihydroartemisinin, amodiaquine and desethylamodiaquine in human plasma for application in clinical pharmacological studies of artesunate-amodiaquine drug combination by Lai CS, Nair NK, Muniandy A, Mansor SM, Olliaro PL, Navaratnam V. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Feb 15; 877(5-6):558-62.
With the expanded use of the combination of artesunate (AS) and amodiaquine (AQ) for the treatment of falciparum malaria and the abundance of products on the market, comes the need for rapid and reliable bioanalytical methods for the determination of the parent compounds and their metabolites. While the existing methods were developed for the determination of either AS or AQ in biological fluids, the current validated method allows simultaneous extraction and determination of AS and AQ in human plasma. The method is sensitive, selective, accurate, reproducible and suited particularly for pharmacokinetic study of AS–AQ drug combination and can also be used to compare the bioavailability of different formulations, including a fixed-dose AS–AQ co-formulation.
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Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal by Brasseur P, Agnamey P, Gaye O, Cisse M, Badiane M, Vaillant M, Taylor WR, Olliaro P. Trop Med Int Health. 2009 Jan; 14(1):79-87.
Several products of artesunate plus amodiaquine (AS + AQ) are being deployed in malaria-endemic countries for treating uncomplicated falciparum malaria but dosing accuracy and consequential effects on efficacy and tolerability have not been examined. Patients were treated and followed by research teams or local health centre staff in Casamance, Senegal. AS + AQ was given as: (i) loose combination (AS 50 mg, AQ 200 mg), dosed on body weight, or (ii) co-blistered product (AS 50 mg, AQ 153 mg) dosed by weight or age. It was concluded that Artesunate is easier to dose than AQ. Currently available age-dosed, co-blistered AS + AQ tends to overdose AQ and is less well tolerated than loose tablets.
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