title: Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon.
abstract: 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.
authors.affiliation: Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon. michael.ramharter@meduniwien.ac.at
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.forename: Florian
authors.initials: F
authors.lastname: Kurth
authors.forename: Annette C
authors.initials: AC
authors.lastname: Schreier
authors.forename: Johannes
authors.initials: J
authors.lastname: Nemeth
authors.forename: Isabelle von
authors.initials: Iv
authors.lastname: Glasenapp
authors.forename: Sabine
authors.initials: S
authors.lastname: Bélard
authors.forename: Meike
authors.initials: M
authors.lastname: Schlie
authors.forename: Judith
authors.initials: J
authors.lastname: Kammer
authors.forename: Philemon Koumba
authors.initials: PK
authors.lastname: Koumba
authors.forename: Badara
authors.initials: B
authors.lastname: Cisse
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Claude
authors.initials: C
authors.lastname: Oeuvray
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fleckenstein
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
mesh_terms: 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
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D009287:Naphthyridines; D000077332:Artesunate; C027871:pyronaridine