Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.

Bearing the increase in antimicrobial resistance as well as the emergence of novel viruses with pandemic potential in mind, it is obvious that development pathways need to be accelerated further. At the same time, attrition risks need to be minimized to allow that drugs reach the patient. For successful translation of novel anti-infectives, several obstacles have to be overcome. This article illustrates recent developments and advances on pharmacokinetic (PK)/pharmacodynamic (PD) methods that can be employed to optimize preclinical development. It specifically emphasizes PK/PD considerations not only for classical antibacterials and antivirals but also for novel approaches, such as proteolysis-targeting chimers, click-to-release systems, or anti-virulence concepts. Particularly, the latter, nontraditional anti-infective solutions pose novel challenges for PK/PD, as development pathways are not yet straightforward. Thus, this article also aims to provide ideas on how to tackle challenging PK/PD aspects of nontraditional anti-infectives, taking advantage and inspiration from traditional development pathways.