Pharmacokinetics of Antimicrobial Drugs

The pharmacokinetics of antimicrobial dmgs is discussed in Chapter 2. The purpose of the following discussion, then, is to introduce the concept of pharmacokinetics and, in particular, to address the consequences of an antimicrobial drug s pKa value for both action on the target pathogen and fate in the body. 

More often than not, the infection site (the biophase) is remote from the circulating blood that is commonly sampled to measure drug concentration. Several authors have reported that plasma concentrations of free (nonprotein-bound) drug are generally the best predictors of the clinical success of antimicrobial therapy. The biophase in most infections comprises extracellular fluid (plasma -f interstitial fluids). Most pathogens of clinical interest are located extracellularly and as a result, plasma concentrations of free drug are generally representative of tissue concentrations however, there are some notable exceptions  

Intracellular microbes such as Lawsonia intracellu-laris, the causative agent of proliferative enteropathy 

Anatomic barriers to the passive diffusion of antimicrobial drugs are encountered in certain tissues, including the central nervous system, the eye, and the prostate gland. 

Pathological barriers such as abscesses impede the passive diffusion of drugs. 

---