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Phage Therapy Pharmacology

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Abstract:

Phage therapy—application of bacteria-specific viruses to reduce densities of pathogenic or nuisance bacteria— is a two-step process involving phage penetration to target bacteria followed by bacteria killing. Any analysis of these steps is inherently ecological as they represent phage-environment interactions, i.e., between phages and bacteria as well as between phages and body tissues. In considering phages more generically, as selectively toxic antibacterial agents employed to treat bacterial infections, the term “ecology” may be fairly cleanly replaced with the term “pharmacology”. Pharmacology, in turn, may be distinguished into two major components: pharmacokinetics and pharmacodynamics. Pharmacokinetics is explicitly a description of the body's impact on a drug (e.g., movement through and between body compartments) whereas pharmacodynamics is a description of a drug's impact on the body. “Body” includes both body tissues and microbial flora, so an important component of antibacterial pharmacodynamics is inhibition of the growth of target bacteria. Our guiding premise is that phage therapy may be rationally improved through a better understanding of phage pharmacokinetics and pharmacodynamics. Our primary conclusions are (i) that the principle advantages of phages, over antibiotics, are the former's relative safety and ease of discovery; (ii) that phage therapy efficacy is highly dependent on attaining relatively high phage “killing titers”; (iii) that attainment of sufficient titers solely via in situ phage replication should, in some or many circumstances, not be counted upon; and (iv) that phage replication nonetheless may provide a “margin of safety” toward attaining phage therapy efficacy.





Keywords: Bacteriophages; ecology; pharmacodynamics; pharmacokinetics

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/138920110790725410

Publication date: January 1, 2010

More about this publication?
  • Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.
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