Pharmacokinetics of ertapenem in colorectal tissue

peer-reviewed
Erstveröffentlichung
2011-12-22Authors
Wittau, Mathias
Scheele, Jan
Bulitta, J. B.
Mayer, Benjamin
Kaever, Volkhard
Wissenschaftlicher Artikel
Published in
Chemotherapy ; 57 (2011), 5. - S. 437-448. - ISSN 0009-3157. - eISSN 1421-9794
Link to original publication
https://dx.doi.org/10.1159/000333377Faculties
Medizinische FakultätInstitutions
UKU. Klinik für Allgemein- und ViszeralchirurgieInstitut für Epidemiologie und Medizinische Biometrie
External cooperations
Medizinische Hochschule HannoverSt. Anna Virngrundklinik
Monash University
Document version
published version (publisher's PDF)Abstract
Background: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. Patients and Methods: Patients ≧18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. Results: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14–15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≧90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT<sub>></sub><sub>MIC</sub> = 20%) and up to 0.25–0.5 mg/l for the near-maximal killing target (40% fT<sub>></sub><sub>MIC</sub>). Conclusion: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously. © In Copyright http://rightsstatements.org/vocab/InC/1.0/
Subject headings
[GND]: Pharmakokinetik | Pharmakodynamik | Lungenentzündung | Ceftriaxon | Carbapename[LCSH]: Drugs; Physiological effect
[MeSH]: Pharmacokinetics | Pharmacological phenomena | Carbapenems | Pneumonia, Ventilator-associated; Drug therapy | Ceftriaxone
[Free subject headings]: Carbapenem | Tissue penetration | Ertapenem | critically-ill patients | complicated intraabdominal infections | healthy-young volunteers | plasma-protein binding | population pharmacokinetics | pharmacodynamics
[DDC subject group]: DDC 610 / Medicine & health
Rights notice
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
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Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-40440
Wittau, Mathias et al. (2021): Pharmacokinetics of ertapenem in colorectal tissue. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-40440
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