Document Detail


Pharmacodynamics of non-replicating viruses, bacteriocins and lysins.
MedLine Citation:
PMID:  17015317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pharmacodynamics of antibiotics and many other chemotherapeutic agents is often governed by a 'multi-hit' kinetics, which requires the binding of several molecules of the therapeutic agent for the killing of their targets. In contrast, the pharmacodynamics of novel alternative therapeutic agents, such as phages and bacteriocins against bacterial infections or viruses engineered to target tumour cells, is governed by a 'single-hit' kinetics according to which the agent will kill once it is bound to its target. In addition to requiring only a single molecule for killing, these agents bind irreversibly to their targets. Here, we explore the pharmacodynamics of such 'irreversible, single-hit inhibitors' using mathematical models. We focus on agents that do not replicate, i.e. in the case of phage therapy, we deal only with non-lytic phages and in the case of cancer treatment, we restrict our analysis to replication of incompetent viruses. We study the impact of adsorption on dead cells, heterogeneity in adsorption rates and spatial compartmentalization.
Authors:
James J Bull; Roland R Regoes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Proceedings. Biological sciences / The Royal Society     Volume:  273     ISSN:  0962-8452     ISO Abbreviation:  Proc. Biol. Sci.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-12-14     Completed Date:  2007-02-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101245157     Medline TA:  Proc Biol Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2703-12     Citation Subset:  IM    
Affiliation:
The Institute for Cellular and Molecular Biology, Section of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, USA.
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / pharmacokinetics
Bacteriocins / pharmacokinetics*
Models, Biological
Mucoproteins / pharmacokinetics*
Protein Binding
Virus Replication
Viruses / metabolism*
Grant Support
ID/Acronym/Agency:
GM57756/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Bacteriocins; 0/Mucoproteins; 0/lysin
Comments/Corrections

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