Similar Piperacillin/Tazobactam Target Attainment in Obese versus Nonobese Patients despite Differences in Interstitial Tissue Fluid Pharmacokinetics.

obesity piperacillin/tazobactam target-site

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
31 Aug 2021
Historique:
received: 10 07 2021
revised: 09 08 2021
accepted: 27 08 2021
entrez: 28 9 2021
pubmed: 29 9 2021
medline: 29 9 2021
Statut: epublish

Résumé

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 (%

Identifiants

pubmed: 34575456
pii: pharmaceutics13091380
doi: 10.3390/pharmaceutics13091380
pmc: PMC8464843
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Freie Universität Berlin
ID : Open Access Funding
Organisme : Bundesministerium für Bildung, Wissenschaft und Forschung
ID : 01E01001

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Auteurs

David Busse (D)

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, Germany.
Graduate Research Training Program PharMetrX, 12169 Berlin, Germany.

Philipp Simon (P)

Department of Anesthesiology, Intensive Care, University of Leipzig Medical Centre, 04103 Leipzig, Germany.
Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany.

David Petroff (D)

Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany.
Clinical Trial Centre Leipzig, University of Leipzig, 04109 Leipzig, Germany.

Christoph Dorn (C)

Institute of Pharmacy, University of Regensburg, 93053 Regensburg, Germany.

Lisa Schmitt (L)

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, Germany.
Graduate Research Training Program PharMetrX, 12169 Berlin, Germany.

Davide Bindellini (D)

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, Germany.
Graduate Research Training Program PharMetrX, 12169 Berlin, Germany.

Alexander Kratzer (A)

Hospital Pharmacy, University Hospital Regensburg, 93053 Regensburg, Germany.

Arne Dietrich (A)

Department of Anesthesiology, Intensive Care, University of Leipzig Medical Centre, 04103 Leipzig, Germany.

Markus Zeitlinger (M)

Department of Clinical Pharmacology, University Medical University of Vienna, 1090 Vienna, Austria.

Wilhelm Huisinga (W)

Institute of Mathematics, University of Potsdam, 14469 Potsdam, Germany.

Robin Michelet (R)

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, Germany.

Hermann Wrigge (H)

Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany.
Department of Anesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112 Halle, Germany.

Charlotte Kloft (C)

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, Germany.

Classifications MeSH