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COMPARATIVE EVALUATION OF PHAMACODYNAMICS AND NEURONAL OXIDATIVE STRESS ELICITED BY LARGE DOSES OF ARTESUNATE IN COMBINATION WITHMEFLOQUINE OR AMODIAQUINE IN Plasmodium berghei INFECTED MICE
Author(s) -
Wilson Francis Daniel Temitope
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.758.41
Subject(s) - artesunate , amodiaquine , plasmodium berghei , pharmacology , medicine , mefloquine , artemisinin , pharmacodynamics , malaria , pharmacokinetics , plasmodium falciparum , immunology
Background: Artemisinins in combination with other conventional antimalarials have been found to elicit greater schizonticidal and gametocidal activity than other antimalarial drugs. However, their pharmacokinetic misfit has raised substantial concerns over their future pharmacodynamic potentials, which include restoration of neutrophil function during covalescence or at full recovery. Method: A total of forty‐five mice (Mean weight = 22.1g) intraperitoneally infected with P. berghei at a dose of 5 × 10 7 parasitized erythrocytes, were randomized into 3 treatment groups of 15 mice per dosing regimen. The animals were scored for mortality, clearance of parasitaemia and pigmented neutrophils. . Results: Administration of escalated doses of artesunate‐amodiaquine and artesunate – mefloquine resulted in dose‐dependent but non significant (P < 0.05) decreases in parasite clearance time (12 – 28.8 h for artesunate + amodiaquine; 16.5 – 27 h for artesunate + mefloquine) and parasite reduction rate (0.65 – 074 % parasite/h and 0.64 −0.78 % parasite/h). While parasitaemia correlated positively but non‐significantly (r = 0.065; P < 0.05), the neutropenia (4472.3 ± 240 vs. 1709.5 ± 17.8 cells/mm3; P < 0.05) and pigmented neutrophils (308.2±2.4 cells/mm3) elicited by P. berghei infection was also not corrected by the two artesunate – based regimens. Conclusion: Based on the results of this study, it can be concluded that the artesunate based combination therapies lack neutrophil restoration ability and oxidative stress corrective function in spite of their antiparasitic efficacy.