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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Preclinical drug evaluation system in the Plasmodium knowlesi baboon model of malaria: The methotrexate study
Journal of Medical Primatology, Volume 42, No. 2, Year 2013
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Description
Background: Drug resistance against first-line antimalarials warrants search for new lead compounds and repurposing of drugs such as methotrexate. Animal models are required for preclinical drug development before clinical testing. This study aimed to develop a preclinical drug development system in baboons infected with Plasmodium knowlesi. Methods: Protocols for drug administration, pharmacokinetics, clinical chemistry and haematology were developed in the baboon model. Baboons were infected with P. knowlesi and methotrexate administered orally for 5 days. Clinical signs, parasitaemia, gross and histopathology examinations were conducted to determine effect of methotrexate in baboons. Results: No major clinical chemistry, haematology and pathological changes attributable to methotrexate were observed. Parasitaemia suppression of 77.67% was achieved at a methotrexate dose of 3.0 mg/kg. Conclusions: A protocol for preclinical drug development in the baboon was optimized. Methotrexate suppressed P. knowlesi malaria in baboons. These findings warrant further characterization of methotrexate for use in combination therapy. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
Authors & Co-Authors
Ichagichu, M.
Kenya, Nairobi
National Museums of Kenya
Ngotho, Maina
Kenya, Nairobi
National Museums of Kenya
Karanja, Simon Muturi
Kenya, Nairobi
Jomo Kenyatta University of Agriculture and Technology
K’okwaro, Gilbert O.
Kenya, Nairobi
Consortium for National Health Research
Kariuki, Thomas M.
Kenya, Nairobi
National Museums of Kenya
Nzila, Alexis M.
Kenya, Nairobi
Kenya Medical Research Institute
Ozwara, Hastings Suba
Kenya, Nairobi
National Museums of Kenya
Statistics
Citations: 7
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1111/jmp.12034
ISSN:
00472565
e-ISSN:
16000684
Research Areas
Infectious Diseases