Impact of Hypothermic Temperature Control on Plasma and Soft Tissue Pharmacokinetics of Penicillin/Beta-Lactamase Inhibitor Combinations in Patients Resuscitated After Cardiac Arrest

URN to cite this document:

urn:nbn:de:bvb:355-epub-765595 Copy

DOI to cite this document:

10.5283/epub.76559 Copy

Stommel, Alexandra-Maria ; Matzneller, Peter ; al Jalali, Valentin ; Wulkersdorfer, Beatrix ; Lackner, Edith ; Mueller, Matthias ; Dorn, Christoph ; Holzer, Michael ; Zeitlinger, Markus

License: Creative Commons Attribution Non-commercial 4.0 PDF - Published Version (1MB)

Date of publication of this fulltext: 14 Apr 2025 07:06

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Details

Item type:	Article
Open Access Type:	CC-License
Journal or Publication Title:	Clinical Pharmacokinetics
Publisher:	Springer Nature Link
Date:	10 April 2025
Institutions:	Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn)
Projects (Historical):	Medical University of Vienna (ICU 13I2, 13I3, 13H1, and 13H3), Medical Scientific Fund of the Mayor of the City Vienna (project number: 15092)
Identification Number:	Value Type 10.1007/s40262-025-01497-1 DOI
Dewey Decimal Classification:	600 Technology > 615 Pharmacy
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Partially
Item ID:	76559

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Abstract

Background and objectives: Penicillin/beta-lactamase inhibitors are often used to treat aspiration pneumonia in patients resuscitated after cardiac arrest (CA). The impact of hypothermic temperature control on the pharmacokinetics of amoxicillin/clavulanate (AMO/CLAV) and ampicillin/sulbactam (AMP/SULB) has not been studied. Our objective was to evaluate the effects of hypothermic temperature ...

Abstract

Background and objectives: Penicillin/beta-lactamase inhibitors are often used to treat aspiration pneumonia in patients resuscitated after cardiac arrest (CA). The impact of hypothermic temperature control on the pharmacokinetics of amoxicillin/clavulanate (AMO/CLAV) and ampicillin/sulbactam (AMP/SULB) has not been studied. Our objective was to evaluate the effects of hypothermic temperature control on the plasma and soft tissue pharmacokinetics of AMO/CLAV and AMP/SULB, including pulmonary concentrations of AMP/SULB, in patients resuscitated after CA.

Methods: This prospective clinical study involved ten adult patients after CA receiving either AMO/CLAV 2 g/0.2 g or AMP/SULB 2 g/1 g intravenously every 8 h. Patients underwent hypothermic temperature control (33 ± 1 °C) for 24 h, followed by normothermia. Plasma, urine, muscle, and subcutaneous pharmacokinetics were measured and plasma protein-binding assessed for each subject. Microdialysis determined unbound drug concentrations in soft tissues. The pulmonary concentration of AMP/SULB was analyzed in the epithelial lining fluid.

Results: No significant differences in plasma pharmacokinetics or renal excretion of AMO/CLAV and AMP/SULB were observed between the two temperature conditions. Soft tissue concentrations showed no consistent trend. Pharmacokinetic/pharmacodynamic targets (time that the unbound plasma concentrations were above the minimal inhibitory concentration [MIC] for MIC up to 8 mg/L) were met but not for 16 mg/L. Pulmonary concentrations of AMP/SULB in the epithelial lining fluid showed no clear trend.

Conclusion: This study indicates that hypothermic temperature control does not significantly affect plasma concentrations, soft tissue concentrations, or renal excretion of AMO/CLAV and AMP/SULB in patients resuscitated after CA. However, pulmonary concentrations of AMP/SULB exhibited interindividual variability.

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Metadata last modified: 14 Apr 2025 07:06

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