Efficacy of novel oral formulations of α/β arteether against multidrug-resistant malaria in mice.

Abstract

BACKGROUND:

alpha/beta arteether (AE), an effective artemisinin derivative, was developed as intramuscular injection for multidrug-resistant (MDR) and severe falciparum malaria, but intramuscular treatment has its own limitations and cannot be given to patients in rural areas where proper hospital facilities are not available and people are reluctant to take injections. Due to widespread occurrence of MDR strains of Plasmodiumfalciparum, an oral AE formulation is urgently needed to cure the malaria patients.

METHODS:

Several AE formulations were prepared and tested orally in Swiss mice infected with MDR P. yoelii nigeriensis at a dose of 50 mg/kg/day for 5 days. The comparative antimalarial efficacy of eight different AE formulations was assessed at different time intervals in treated and control animals.

RESULTS:

Three new AE formulations, namely AE F-2, F-10B and F-14, were found to have 100% curative antimalarial activity in an experimental model, as shown by survival of treated animals beyond 28 days, with no recrudescence of parasitemia being recorded. Another two formulations, AE F-8 and F-9B, produced 96-97% cure.

CONCLUSION:

Five alpha/beta AE formulations (F-2, F-10B, F-8, F-9B and F-14) can be considered potential candidates for further drug development. AE F-14, a solid dosage form of AE prepared by completely removing oil and incorporating 0.2% cholesterol, is a new promising lead, even in pediatric malaria, which can reduce the neurotoxic potential of AE and other artemisinin derivatives.

• Authors: Renu Tripathi, Madhu Khanna, Anil Kumar Dwivedi
• Journal: Chemotherapy (Chemotherapy) Vol. 56 Issue 3 Pg. 178-83 ( 2010) ISSN: 1421-9794 [Electronic] Switzerland
• PMID: 20501998 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2010 S. Karger AG, Basel.

Chemical References

• Antimalarials
• Artemisinins
• artemotil

Topics

• Administration, Oral
• Animals
• Antimalarials (administration & dosage, chemistry)
• Artemisinins (administration & dosage, chemistry)
• Drug Resistance, Multiple (drug effects, physiology)
• Female
• Isomerism
• Malaria (drug therapy, physiopathology)
• Male
• Mice
• Plasmodium yoelii (drug effects, physiology)