Abstract

Malaria remains a threat to human life and a burden to the global economy due to the emergence of drug-resistant malaria parasites. Thus, the development of an effective anti-malarial drug is required. CN005M and MeCN05M were evaluated. Wister rats were grouped into two groups (n=6) and administered 10 mg/kg bw of CN005M or MeCN005M. Plasma was analyzed using HPLC. CN005M volume of distribution (34.96 ± 7.04) was non-significantly (P > 0.05) changed when compared to MeCN005M (27.33 ± 0.08). CN005M and MeCN005M Mean Retention Time resided non-significantly (P > 0.05) for a period of 9.90 and 12.77 h respectively in the body. Cmax value of CN005M (0.42 μg/mL) was significantly higher (P < 0.05) when compared to the equivalent dose of the MeCN005M (0.24 μg/mL). CN005M (0.50 h) significantly (P < 0.05) reached Tmax sixteen (16) fold faster
compared to MeC005M (8.00 h). There was a significant (P < 0.05) reduction in drug clearance and increased last measurable plasma concentration in MeCN005M when compared to CN005M. The results indicate MeCN005M has a lower Cmax with an extended Tmax, with a low toxicity threshold and sustained efficacy. MeCN005M may provide the benefits of reducing the required dose and frequency while maintaining therapeutic efficacy.

Key words: Antimalarial, Pharmacokinetic, CN005M, Drug modification, Drug discovery