Preclinical drug evaluation system in the Plasmodium knowlesi baboon model of malaria: the methotrexate study
Article first published online: 7 JAN 2013
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Journal of Medical Primatology
Volume 42, Issue 2, pages 62–70, April 2013
How to Cite
Ichagichu, M., Ngotho, M., Karanja, S.M., Kokwaro, G., Kariuki, T., Nzila, A. and Ozwara, H. (2013), Preclinical drug evaluation system in the Plasmodium knowlesi baboon model of malaria: the methotrexate study. Journal of Medical Primatology, 42: 62–70. doi: 10.1111/jmp.12034
- Issue published online: 6 MAR 2013
- Article first published online: 7 JAN 2013
- Manuscript Accepted: 10 DEC 2012
- AntiMal Consortium. Grant Number: 018834
- drug repurposing;
- malaria therapy;
- Olive baboon (Papio cynocephalus anubis);
- Plasmodium knowlesi
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.
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.
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.
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.