A Pharmacokinetic Study of Antimalarial 3,5-Diaryl-2-aminopyridine DerivativesReport as inadecuate

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Malaria Research and Treatment - Volume 2015 2015, Article ID 405962, 5 pages -

Research Article

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory, Cape Town 7925, South Africa

Department of Chemistry, University of Cape Town, Rondebosch, Cape Town 7700, South Africa

Received 5 January 2015; Revised 16 March 2015; Accepted 18 March 2015

Academic Editor: Neena Valecha

Copyright © 2015 Ntokozo Dambuza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Malaria caused by Plasmodium falciparum is responsible for approximately 80% of the incidence and 90% of deaths which occur in the World Health Organization WHO African region, with children and pregnant women having the highest incidence. P. falciparum has developed resistance, and therefore new effective candidate antimalarial drugs need to be developed. Previous studies identified 3,5-diaryl-2-aminopyridines as potential antimalarial drug candidates; therefore, derivatives of these compounds were synthesized in order to improve their desired properties and pharmacokinetic PK properties of the derivatives were investigated in a mouse model which was dosed orally and intravenously. Collected blood samples were analyzed using liquid chromatography coupled to mass spectrometer LC-MS-MS. The mean peak plasma level of 1.9 μM was obtained at 1 hour for compound 1 and 3.3 μM at 0.5 hours for compound 2. A decline in concentration was observed with a half-life of 2.53 and 0.87 hours for compound 1 in mice dosed orally and intravenously, respectively. For compound 2 a half-life of 2.96 and 0.68 hours was recorded. The bioavailability was 69% and 59.7% for compound 1 and compound 2, respectively.

Author: Ntokozo Dambuza, Peter Smith, Alicia Evans, Dale Taylor, Kelly Chibale, and Lubbe Wiesner

Source: https://www.hindawi.com/


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