Pharmacokinetics of two paediatric artesunate mefloquine drug formulations in the treatment of uncomplicated falciparum malaria in Gabon.
OBJECTIVE
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.


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) (2,050 and 2,470 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 (2,550 and 1,815 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.
Ramharter
Michael
M
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon. michael.ramharter@meduniwien.ac.at
Kurth
Florian M
FM
Bélard
Sabine
S
Bouyou-Akotet
Marielle K
MK
Mamfoumbi
Modeste Mabika
MM
Agnandji
Selidji T
ST
Missinou
Michel A
MA
Adegnika
Ayola A
AA
Issifou
Saadou
S
Cambon
Nathalie
N
Heidecker
János L
JL
Kombila
Maryvonne
M
Kremsner
Peter G
PG
D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005681:Gabon; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D013607:Tablets; D000077332:Artesunate; D015767:Mefloquine