Open Access Highly Accessed Review

Review of pyronaridine anti-malarial properties and product characteristics

Simon L Croft1*, Stephan Duparc2, Sarah J Arbe-Barnes3, J Carl Craft4, Chang-Sik Shin5, Lawrence Fleckenstein6, Isabelle Borghini-Fuhrer2 and Han-Jong Rim7

Author Affiliations

1 Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

2 Medicines for Malaria Venture, Geneva, Switzerland

3 Aptiv Solutions, Stevenage BioScience Catalyst, Stevenage, SG1 2FX, UK

4 Former MMV Chief Scientific Officer, Libertyville, IL, USA

5 Shin Poong Pharmaceuticals Co Ltd, Seoul, Republic of Korea

6 College of Pharmacy, University of Iowa, Iowa City, IA, USA

7 Department of Parasitology, College of Medicine, Korea University, Seoul, Korea

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Malaria Journal 2012, 11:270  doi:10.1186/1475-2875-11-270

Published: 9 August 2012

Abstract

Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure.

Keywords:
Pyronaridine; Plasmodium falciparum; Plasmodium vivax; Review; Artemisinin containing compound; Anti-malarial therapy