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Title: Pharmacokinetic-pharmacodynamic parameters in the empiric treatment of bacterial infections using chemotherapeutics as an example
Abstract:
The aim of the thesis was to develop a therapeutic algorithm for the management of bacterial infections using phannacokinetic-pharmacodynamic data as indicators of efficacy and safety of pharmacotherapy in order to optimize dosage regimens of the selected antibacterial agents. The following data were taken into account: maximum serum drug concentration/MIC90 ratio (Cmax/MIC90) or twenty-four-hour area under the concentration-time curve/MIC90 (AUC0-24/MIC90) for antibacterial agents exerting concentrationdependent killing (ciprofloxacin CPX, aminoglycoside antibiotics) and the time during which serum drug concentration exceeds MIC90 (tc>MIC) for antibiotics exhibiting time-dependent killing (cefuroxim CFU). To achive this goal, the analytical methods to detennine CPX, CFU and aminoglycosides were validated. Pharmacokinetics of these drugs in pathophysiological conditions was assessed. PK/PD parameters were estimated in the patient populations studied and the efficacy of dosage regimen based on PK/PD criteria was predicted in relatin to main pathogenes responsible for lower respiratory tract infections such as Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa. Consequently, the drug dosage usually used was modified. The results of this study indicated that there was large variability in ; pharmacokinetic parameters of antibacterial agents under investigation. The most important factor leading to this variability was age (first of all for CFU) accompanied by renal insufficiency (for CPX and CFU). In addition, the present study revealed that both PK/PD parameters (Cmax/MIC90, AUC0-24/MIC90, tc>MIC) and MIC breakpoints may used as the equivalent methods for the prediction of the antibioticotherapy efficacy. Taking into account PK/PD criteria, the usually used dosage regimens of the antibacterial drugs studied would require dosage individualization in most patients from both therapeutic and economic standpoints.
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Last modified:
Jul 7, 2022
In our library since:
Nov 21, 2012
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17
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All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/1350
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| Edition name | Date |
|---|---|
| ZB-99181 | Jul 7, 2022 |
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