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Leishmania and other intracellular pathogens: selectivity, drug distribution and PK–PD

[BSP Autumn Symposium “Microbial protein targets: towards understanding and intervention”, 14th–16th September 2016, University of Durham UK]

Published online by Cambridge University Press:  06 October 2017

SIMON L. CROFT
SIMON L. CROFT*
Affiliation:
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
*
*Corresponding author: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. E-mail: simon.croft@lshtm.ac.uk
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Summary

New drugs and treatments for diseases caused by intracellular pathogens, such as leishmaniasis and the Leishmania species, have proved to be some of the most difficult to discover and develop. The focus of discovery research has been on the identification of potent and selective compounds that inhibit target enzymes (or other essential molecules) or are active against the causative pathogen in phenotypic in vitro assays. Although these discovery paradigms remain an essential part of the early stages of the drug R & D pathway, over the past two decades additional emphasis has been given to the challenges needed to ensure that the potential anti-infective drugs distribute to infected tissues, reach the target pathogen within the host cell and exert the appropriate pharmacodynamic effect at these sites. This review will focus on how these challenges are being met in relation to Leishmania and the leishmaniases with lessons learned from drug R & D for other intracellular pathogens.

Keywords

Leishmaniapharmacodynamicspharmacokineticsdrug distribution
Type
Special Issue Review
Information
Parasitology , Volume 145 , Special Issue 2: Microbial protein targets: towards understanding and intervention , February 2018 , pp. 237 - 247
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Copyright © Cambridge University Press 2017 

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