[e-drug] Pharmacokinetics of paediatric antimalarials

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: Pharmacokinetics of paediatric antimalarials
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Ramharter M, Kurth FM, Bélard S, Bouyou-Akotet MK, Mamfoumbi MM,
Agnandji ST, Missinou MA, Adegnika AA, Issifou S, Cambon N, Heidecker
JL, Kombila M, Kremsner PG. Pharmacokinetics of two paediatric
artesunate mefloquine drug formulations in the treatment of
uncomplicated falciparum malaria in Gabon. J Antimicrob Chemother. 2007
Nov;60(5):1091-6. Epub 2007 Sep 19.

Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.

Objectives. Paediatric drug formulations of artemisinin combination
therapies and pharmacokinetic data supporting their use in African
children are urgently needed for the effective treatment of young
children suffering from falciparum malaria in sub-Saharan Africa. 

Patients and methods. In this study, the pharmacokinetic characteristics
of a novel paediatric granule formulation of artesunate-mefloquine
therapy were evaluated in comparison to the standard tablet formulation
in the treatment of uncomplicated malaria in paediatric patients.
Twenty-four patients were assigned to treatment according to body weight
with either a fixed-dose paediatric granule co-formulation (10-20 kg
body weight) or a free-dose co-blister tablet formulation of
artesunate-mefloquine (>20-40 kg body weight). 
Results. Median values for C(max) (861 and 930 ng/mL), T(max) (1.5 and
1.5 h) and AUC(0-)(t) (2050 and 2470 ng.h/mL) were comparable for
dihydroartemisinin in the two groups. Exploratory analysis of mefloquine
plasma levels revealed a trend towards higher concentrations in the
younger age group during the absorption phase (2550 and 1815 ng/mL, 54 h
after initiation of treatment, respectively). Median mefloquine
concentrations at day 28 were 197 and 343 ng/mL, respectively. 

Conclusions. The pharmacokinetic characteristics of the two paediatric
dosage forms, i.e. the novel fixed-dose co-formulation and the standard
co-blister of artesunate-mefloquine show comparable results in the two
treatment groups. The novel fixed-dose paediatric formulation is an
interesting option for outpatient treatment of uncomplicated malaria in
African children.