Basics of phage therapy pharmacology. Absorption and distribution can have the effect of increasing antibacterial concentrations within the vicinity of target bacteria, though also they have a diluting effect on dosages. Phage infection too can increase phage numbers within the vicinity of target bacteria, which I have indicated as being an aspect of metabolism and which more generally is a description of the chemical modification of a drug. Together these pharmacokinetic mechanisms contribute to some peak phage density that may or may not be sufficient to substantially decrease densities of target bacteria [93, 117]. Particularly, peak densities must exceed some minimum effective concentration to effect net reductions in bacterial densities and these densities can be achieved through a combination of supplying sufficient phage numbers per individual dose, supplying multiple doses, and/or allowing for phages to replicate in situ. Ideally phage densities will not be so high that toxicity results. Exactly what phage densities are necessary to achieve toxicities is not well appreciated, except that impurities in phage formulations can contribute to such toxicities (as too can potentially the humoral immune system given nonnaive patients). As a consequence of this uncertainty, what constitutes a preferred upper limit of phage densities is not known in the same way that minimum toxic concentrations can be appreciated for specific small-molecule drugs, except that this upper limit may be high relative to minimum effective phage densities. Lastly, various mechanisms exist whereby phage densities may decrease over time, which include what pharmacologically are described as metabolism and excretion, though as noted dosage dilution plays a role as well. A modified version of this figure is found in Abedon [93] as well.
