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.
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: Selidji T Agnandji; Florian Kurth; Jose F Fernandes; Solange S Soulanoudjingar; Beatrice P Abossolo; Ghyslain Mombo-Ngoma; Arti Basra; Raquel González; Gondo Kizito; Pembe I Mayengue; Lorenz Auer-Hackenberg; Saadou Issifou; Bertrand Lell; Ayola A Adegnika; Michael Ramharter Journal: Malar J Date: 2011-12-14 Impact factor: 2.979
Authors: Sophie H Adjalley; Geoffrey L Johnston; Tao Li; Richard T Eastman; Eric H Ekland; Abraham G Eappen; Adam Richman; B Kim Lee Sim; Marcus C S Lee; Stephen L Hoffman; David A Fidock Journal: Proc Natl Acad Sci U S A Date: 2011-10-31 Impact factor: 11.205
Authors: Marielle K Bouyou-Akotet; Michael Ramharter; Edgard Brice Ngoungou; Modeste Mabika Mamfoumbi; Mireille Pemba Mihindou; Michel A Missinou; Florian Kurth; Sabine Bélard; Selidji T Agnandji; Saadou Issifou; János L Heidecker; Sonja Trapp; Peter G Kremsner; Maryvonne Kombila Journal: Wien Klin Wochenschr Date: 2010-03 Impact factor: 1.704
Authors: R N Price; J Marfurt; F Chalfein; E Kenangalem; K A Piera; E Tjitra; N M Anstey; B Russell Journal: Antimicrob Agents Chemother Date: 2010-09-27 Impact factor: 5.191