Current status of malaria chemotherapy and the role of pharmacology in antimalarial drug research and development
- 30 July 2009
- journal article
- review article
- Published by Wiley in Fundamental & Clinical Pharmacology
- Vol. 23 (4) , 387-409
- https://doi.org/10.1111/j.1472-8206.2009.00709.x
Abstract
Antimalarial drugs have played a mainstream role in controlling the spread of malaria through the treatment of patients infected with the plasmodial parasites and controlling its transmissibility. The inadequate armory of drugs in widespread use for the treatment of malaria, development of strains resistant to currently used antimalarials, and the lack of affordable new drugs are the limiting factors in the fight against malaria. In addition, other problems with some existing agents include unfavorable pharmacokinetic properties and adverse effects/toxicity. These factors underscore the continuing need of research for new classes of antimalarial agents, and a re-examination of the existing antimalarial drugs that may be effective against resistant strains. In recent years, major advances have been made in the pharmacology of several antimalarial drugs both in pharmacokinetics and pharmacodynamics aspects. These include the design, development, and optimization of appropriate dosage regimens of antimalarials, basic knowledge in metabolic pathways of key antimalarials, as well as the elucidation of mechanisms of action and resistance of antimalarials. Pharmacologists have been working in close collaboration with scientists in other disciplines of science/biomedical sciences for more understanding on the biology of the parasite, host, in order to exploit rational design of drugs. Multiple general approaches to the identification of new antimalarials are being pursued at this time. All should be implemented in parallel with focus on the rational development of new agents directed against newly identified parasite targets. With major advances in our understanding of malaria parasite biology coupled with the completion of the malaria genome, has presented exciting opportunities for target-based antimalarial drug discovery.Keywords
This publication has 196 references indexed in Scilit:
- Evidence of Artemisinin-Resistant Malaria in Western CambodiaNew England Journal of Medicine, 2008
- Malaria research in the post-genomic eraNature, 2008
- New antimalarial targets: The example of glucose transportTravel Medicine and Infectious Disease, 2008
- Advances in understanding the genetic basis of antimalarial drug resistanceCurrent Opinion in Microbiology, 2007
- Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignanciesProceedings of the National Academy of Sciences, 2007
- Rectal Administration of Artemisinin Derivatives for the Treatment of MalariaJAMA, 2007
- Investigation of the immunosuppressive activity of artemether on T‐cell activation and proliferationBritish Journal of Pharmacology, 2007
- PfCRT and the trans‐vacuolar proton electrochemical gradient: regulating the access of chloroquine to ferriprotoporphyrin IXMolecular Microbiology, 2006
- Resisting resistance: dealing with the irrepressible problem of malariaBritish Journal of Clinical Pharmacology, 2006
- Artemisinins target the SERCA of Plasmodium falciparumNature, 2003