Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon

J Infect Dis. 2008 Sep 15;198(6):911-9. doi: 10.1086/591096.


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.

Trial registration: NCT00331136.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antimalarials / therapeutic use*
  • Artemisinins / therapeutic use*
  • Artesunate
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Drug Tolerance
  • Female
  • Gabon
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Male
  • Naphthyridines / therapeutic use*
  • Plasmodium falciparum / genetics
  • Polymerase Chain Reaction
  • Safety
  • Treatment Outcome


  • Antimalarials
  • Artemisinins
  • Naphthyridines
  • Artesunate
  • pyronaridine

Associated data