Busse, David and Simon, Philipp and Petroff, David and Dorn, Christoph and Schmitt, Lisa and Bindellini, Davide and Kratzer, Alexander and Dietrich, Arne and Zeitlinger, Markus and Huisinga, Wilhelm and Michelet, Robin and Wrigge, Hermann and Kloft, Charlotte (2021) Similar Piperacillin/Tazobactam Target Attainment in Obese versus Nonobese Patients despite Differences in Interstitial Tissue Fluid Pharmacokinetics. PHARMACEUTICS, 13 (9): 1380. ISSN , 1999-4923
Full text not available from this repository. (Request a copy)Abstract
Precision dosing of piperacillin/tazobactam in obese patients is compromised by sparse information on target-site exposure. We aimed to evaluate the appropriateness of current and alternative piperacillin/tazobactam dosages in obese and nonobese patients. Based on a prospective, controlled clinical trial in 30 surgery patients (15 obese/15 nonobese; 0.5-h infusion of 4 g/0.5 g piperacillin/tazobactam), piperacillin pharmacokinetics were characterized in plasma and at target-site (interstitial fluid of subcutaneous adipose tissue) via population analysis. Thereafter, multiple 3-4-times daily piperacillin/tazobactam short-term/prolonged (recommended by EUCAST) and continuous infusions were evaluated by simulation. Adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target-attainment (PTA >= 90%) based on time unbound piperacillin concentrations exceed the minimum inhibitory concentration (MIC) during 24 h (%fT(>MIC)). Lower piperacillin target-site maximum concentrations in obese versus nonobese patients were explained by the impact of lean (approximately two thirds) and fat body mass (approximately one third) on volume of distribution. Simulated steady-state concentrations were 1.43-times, 95%CI = (1.27; 1.61), higher in plasma versus target-site, supporting targets of %fT(>2xMIC) instead of %fT(>4xMIC) during continuous infusion to avoid target-site concentrations constantly below MIC. In all obesity and renally impairment/hyperfiltration stages, at MIC = 16 mg/L, adequate PTA required prolonged (thrice-daily 4 g/0.5 g over 3.0 h at %fT(>MIC) = 50) or continuous infusions (24 g/3 g over 24 h following loading dose at %fT(>MIC) = 98) of piperacillin/tazobactam.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CRITICALLY-ILL PATIENTS; PROLONGED-INFUSION; POPULATION PHARMACOKINETICS; TAZOBACTAM; ANTIBIOTICS; RISK; PHARMACODYNAMICS; MICRODIALYSIS; INFECTIONS; OVERWEIGHT; piperacillin; tazobactam; target-site; obesity |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 14:10 |
| Last Modified: | 13 Sep 2022 14:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47373 |
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