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Pharmacokinetic-pharmacodynamic modeling of the antibiotic effect of piperacillin in vitro
A Nolting1, T Dalla Costa, K H Rand
1Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
Purpose:
It was the aim of the present study to investigate the in vitro antimicrobial effects of the beta-lactam antibiotic piperacillin on Escherichia coli using concentration-time profiles similar to those encountered in vivo.
Methods:
An in vitro dilution model was used to expose E. coli to various piperacillin concentration profiles. The antimicrobial effect was evaluated by determination of the number of bacteria over time.
Results:
A modified Emax-model was found appropriate to describe the pharmacodynamic effect. This model was linked with the respective piperacillin concentrations to provide a suitable pharmacokinetic-pharmacodynamic (PK-PD) model. The average growth half-life in absence of piperacillin was 28 min and the maximum kill half-life was 25 min. The EC50 for the various dosing regimens averaged 5.2 micrograms/mL and was independent of dose. These parameters were used the simulate the bacterial effects of commonly administered doses or dosing regimens in humans.
Conclusions:
Based on the in vitro data a more frequent administration of piperacillin will be more efficacious. The proposed PK-PD-model allows a more detailed evaluation of dosing regimens than the use of minimum inhibitory concentrations.