Time course of the pharmacokinetics of active phage therapy. Numerous pharmacokinetic processes–either through dilution, inactivation, or inefficiencies in penetration–have the effect of reducing phage densities in situ such as below minimum effective phage densities (MEPDs). These losses may be minimized by reducing the length of the chain of processes separating phage application from phage contact with target bacteria or instead can be addressed by supplying more phages, such as to counteract inevitable losses. Metabolism as a pharmacokinetic process, in the form of phage replication and therefore in situ amplification in density (auto dosing), can reverse these losses and allow an achievement of MEPDs, at least local to target bacteria. The process illustrated in the figure is an elaboration on the concept that otherwise has been described as active treatment, that is, supplying insufficient phage numbers through traditional dosing to achieve MEPDs, and thus relying on active phage replication instead to achieve these densities.
