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: Michael Ramharter, Florian Kurth, Annette C Schreier, Johannes Nemeth, Isabelle von Glasenapp, Sabine Bélard, Meike Schlie, Judith Kammer, Philemon Koumba Koumba, Badara Cisse, Benjamin Mordmüller, Bertrand Lell, Saadou Issifou, Claude Oeuvray, Lawrence Fleckenstein, Peter G Kremsner
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 198 Issue 6 Pg. 911-9 (Sep 15 2008) ISSN: 0022-1899 [Print] United States
• PMID: 18694333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Artemisinins
• Naphthyridines
• Artesunate
• pyronaridine

Topics

• 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