New Antibiotics in Pulmonary and Critical Care Medicine

†, * University of the Pacific, School of Pharmacy Stockton, California, and Kendle International, Inc.;   †Maine Medical Center, Portland, Maine, and University of Vermont, College of Medicine, Burlington, Vermont

Semin Respir Crit Care Med. 2000;21(1) 

In This Article

Protein Binding And Pharmacodynamics

Because the ultimate goal of antimicrobial therapy is to eliminate microorganisms from specific sites of infection, consideration of the effect of an antibiotic's protein binding on this process seems reasonable. In the body, antibiotics exist in an equilibrium of free drug and drug bound to protein. Free drug moves readily from the central blood compartment into the extravascular spaces, whereas protein-bound drug cannot cross capillary walls and remains in the central compartment.[15,16] Moreover, it has been established that only free drug is pharmacologically active.[17,18,19]

The affect of protein binding on the efficacy of antibiotics is a controversial issue. Excessively high (greater than 85 to 90%) protein binding has been shown to have an adverse impact on the microbiological activity of various antibiotics when used clinically to treat infections caused by organisms that were susceptible in vitro.[20.21] On the other hand, an agent that is highly protein bound may still exhibit excellent clinical efficacy because of favorable pharmacokinetics and compensational microbiological activity.[22] One must remember that in vitro susceptibility testing does not account for protein binding in vivo and total serum concentrations reflect both bound and unbound drug.

When pharmacodynamic relationships are described mathematically and quantified as ratios or measurements (e.g., Cp:MIC, AUC:MIC, or time > MIC), it is sensible to incorporate the degree of protein into these calculations. This is logical given that the AUC of free drug in serum approximates that found in the interstitial fluid, the site of most bacterial infections. For instance, it is useful to consider the degree of protein binding when doing intraquinolone pharmacodynamic comparisons, for this may lead to more clinically relevant conclusions.

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