Pharmacodynamics

A true understanding of the pharmacodynamics begins with a few basic principles. First, administering a fixed dose of drug to a large number of patients will result in substantially different profiles of changing concentrations of the drug over time (i.e., variability in pharmacokinetics). Second, the shape of the curve describing the concentration-time profile can have a direct impact on the effect of a particular drug dose (i.e., different drugs have different pharmacodynamic properties). Only free (non-protein bound) drug is microbiologically active. The higher the value of the measure of the potency of the drug [e.g., the minimum inhibitory concentration (MIC)] for the pathogen, the less effect a fixed drug exposure will have, and finally, it is the drug exposure at the site of the infection which is responsible for the antimicrobial effect. With respect to the latter, most pharmacodynamic studies reference drug exposure in blood to an effect that takes place at the site of infection (e.g., lung epithelial lining fluid, tissue, bone, etc). For most antibiotics, including β-lactams, the exposure at the site of infection is similar to that of blood, and therefore, blood is a reasonable surrogate marker for exposure. However, one must consider each antibiotics pharmacokinetic characteristic to determine if this relationship will hold true.

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Last date updated on September, 2024