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Scripta Scientifica Medica

New approaches to optimizing antibacterial therapy: Pk/Pd parameters

Maria D. Zhelyazkova-Savova


Optimization of the antibacterial therapy constitutes an important clinical problem. A new possibility to solve it is to consider the pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs in their unity. PK of antimicrobials has always been a significant factor in the drug choice, since it determines the accumulation of the drug at the site of infection. The current aspects of PD of antibacterial drugs, however, are only lately being intensively developed. Amongst the PD indices, only MIC (reflecting the susceptibility of the infective agent to drugs) has been routinely used in the clinical practice up to now. Currently, increasing attention is being paid to other PD parameters: pattern of bacterial killing (time- or concentration dependent) and persistent (post-an ti bi otic) ef fect. According to these parameters, antibacterial drugs can be classified into three groups. Combining the PK indices maximal plasma concentration (Cmax) and area under concentration-time curve (AUC) with PD ones (MIC) in a way based on experimental evidence, allows the development of integral PK/PD parameters, predicting clinical and efficacy and bacteriological cure.Forbeta-lactams and macrolides such a parameter is the time during which the concentration of the drug is higher than MIC (T>MIC90). With aminoglycosides and fluoroquinolones, the parameter correlating bets with positive outcomes, ate the ratios Cmax/MIC90 and AUC24/MIC90. With azalides the best predictor of efficacy is AUC24/MIC90. The introduction of PK/PG parameters in clinical performance has the potential to provide individual approaches in the choice of antibacterial drug and their dosing regimen. They can also contribute to reducing resistance and adverse effects, as well as to lowering the cost of therapy.

Scripta Scientifica Medica 2007;39(1):19-23

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About The Author

Maria D. Zhelyazkova-Savova
Medical University of Varna

Department of Preclinical and Clinical Pharmacology

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