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


CONCLUSIONS
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.
Tripathi
Renu
R
Division of Parasitology, Central Drug Research Institute, Lucknow, India. renu1113@rediffmail.com
Khanna
Madhu
M
Dwivedi
Anil Kumar
AK
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007536:Isomerism; D008288:Malaria / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000502:physiology
D000962:Antimalarials; D037621:Artemisinins; C055141:artemotil