Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon.
BACKGROUND
The development of novel artemisinin-combination therapies suitable for the treatment of pediatric patients suffering from malaria is a research priority. The aim of this study was to investigate a novel fixed-dose pyronaridine-artesunate combination for the treatment of uncomplicated falciparum malaria in Gabonese patients 2-14 years old.


METHODS
The study was designed as an open-label dose-escalation study recruiting 60 pediatric patients sequentially in 4 treatment cohorts: study drugs were administered once daily for 3 days, as tablet coformulations (pyronaridine:artesunate ratios of 6:2, 9:3, and 12:4 mg/kg) and as a granule coformulation (pyronaridine:artesunate ratio of 9:3 mg/kg). The primary end points were tolerability, safety, and pharmacokinetics of pyronaridine-artesunate treatment. Efficacy was treated as a secondary outcome measure.


RESULTS
The drugs had a good tolerability and safety profile, at all dose levels. Pharmacokinetic analysis revealed a dose-dependent increase in the maximum plasma/blood concentration and the area under the curve, as well as comparable relative bioavailability for the granule coformulation. Polymerase chain reaction-corrected cure rates at day 28 were 100% in per-protocol analysis, at all dose levels.


CONCLUSIONS
Pyronaridine-artesunate is a promising novel artemisinin-combination therapy for pediatric patients with uncomplicated Plasmodium falciparum malaria, and the development of both the tablet and the granule coformulations is warranted.
Ramharter
Michael
M
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon. michael.ramharter@meduniwien.ac.at
Kurth
Florian
F
Schreier
Annette C
AC
Nemeth
Johannes
J
Glasenapp
Isabelle von
Iv
Bélard
Sabine
S
Schlie
Meike
M
Kammer
Judith
J
Koumba
Philemon Koumba
PK
Cisse
Badara
B
Mordmüller
Benjamin
B
Lell
Bertrand
B
Issifou
Saadou
S
Oeuvray
Claude
C
Fleckenstein
Lawrence
L
Kremsner
Peter G
PG
D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D005681:Gabon; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D009287:Naphthyridines / Q000627:therapeutic use*; D010963:Plasmodium falciparum / Q000235:genetics; D016133:Polymerase Chain Reaction; D012449:Safety; D016896:Treatment Outcome
D000962:Antimalarials; D037621:Artemisinins; D009287:Naphthyridines; D000077332:Artesunate; C027871:pyronaridine