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Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis

BACKGROUND AND OBJECTIVE: Tigecycline, a broad-spectrum glycylcycline antibiotic, is approved for use at a fixed dose irrespective of body weight. However, its pharmacokinetics may be altered in obesity, which would impact on the antibiotic’s effectiveness. The objective of this study was to investi...

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Autores principales: Dorn, Christoph, Petroff, David, Kratzer, Alexander, Kees, Frieder, Kloft, Charlotte, Zeitlinger, Markus, Wrigge, Hermann, Simon, Philipp
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399032/
https://www.ncbi.nlm.nih.gov/pubmed/35945479
http://dx.doi.org/10.1007/s13318-022-00789-2
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author Dorn, Christoph
Petroff, David
Kratzer, Alexander
Kees, Frieder
Kloft, Charlotte
Zeitlinger, Markus
Wrigge, Hermann
Simon, Philipp
author_facet Dorn, Christoph
Petroff, David
Kratzer, Alexander
Kees, Frieder
Kloft, Charlotte
Zeitlinger, Markus
Wrigge, Hermann
Simon, Philipp
author_sort Dorn, Christoph
collection PubMed
description BACKGROUND AND OBJECTIVE: Tigecycline, a broad-spectrum glycylcycline antibiotic, is approved for use at a fixed dose irrespective of body weight. However, its pharmacokinetics may be altered in obesity, which would impact on the antibiotic’s effectiveness. The objective of this study was to investigate the plasma and subcutaneous tissue concentrations of tigecycline in obese patients compared with those in a non-obese control group. METHODS: Fifteen obese patients (one class II and 14 class III) undergoing bariatric surgery and 15 non-obese patients undergoing intra-abdominal surgery (mainly tumour resection) received a single dose of 50 or 100 mg tigecycline as an intravenous short infusion. Tigecycline concentrations were measured up to 8 h after dosing in plasma (total concentration), in ultrafiltrate of plasma (free concentration), and in microdialysate from subcutaneous tissue, respectively. RESULTS: In obese patients, total peak plasma concentration (1.31 ± 0.50 vs 2.27 ± 1.40 mg/L) and the area under the concentration–time curve from 0 to 8 h (AUC(8h,plasma): 2.15 ± 0.42 vs 2.74 ± 0.73 h⋅mg/L), as normalized to a 100 mg dose, were significantly lower compared with those of non-obese patients. No significant differences were observed regarding the free plasma concentration, as determined by ultrafiltration, or the corresponding AUC(8h) (fAUC(8h,plasma)). Concentrations in interstitial fluid (ISF) of subcutaneous tissue were lower than the free plasma concentrations in both groups, and they were lower in obese compared to non-obese patients: the AUC(8h) in ISF (AUC(8h,ISF)) was 0.51 ± 0.22 h⋅mg/L in obese and 0.79 ± 0.23 h⋅mg/L in non-obese patients, resulting in a relative tissue drug exposure (AUC(8h,ISF)/fAUC(8h,plasma)) of 0.38 ± 0.19 and 0.63 ± 0.24, respectively. CONCLUSION: Following a single dose of tigecycline, concentrations in the ISF of subcutaneous adipose tissue are decreased in heavily obese subjects, calling for an increased loading dose. EU CLINICAL TRIALS REGISTRATION NUMBER: EudraCT No. 2012-004383-22. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13318-022-00789-2.
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spelling pubmed-93990322022-08-25 Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis Dorn, Christoph Petroff, David Kratzer, Alexander Kees, Frieder Kloft, Charlotte Zeitlinger, Markus Wrigge, Hermann Simon, Philipp Eur J Drug Metab Pharmacokinet Short Communication BACKGROUND AND OBJECTIVE: Tigecycline, a broad-spectrum glycylcycline antibiotic, is approved for use at a fixed dose irrespective of body weight. However, its pharmacokinetics may be altered in obesity, which would impact on the antibiotic’s effectiveness. The objective of this study was to investigate the plasma and subcutaneous tissue concentrations of tigecycline in obese patients compared with those in a non-obese control group. METHODS: Fifteen obese patients (one class II and 14 class III) undergoing bariatric surgery and 15 non-obese patients undergoing intra-abdominal surgery (mainly tumour resection) received a single dose of 50 or 100 mg tigecycline as an intravenous short infusion. Tigecycline concentrations were measured up to 8 h after dosing in plasma (total concentration), in ultrafiltrate of plasma (free concentration), and in microdialysate from subcutaneous tissue, respectively. RESULTS: In obese patients, total peak plasma concentration (1.31 ± 0.50 vs 2.27 ± 1.40 mg/L) and the area under the concentration–time curve from 0 to 8 h (AUC(8h,plasma): 2.15 ± 0.42 vs 2.74 ± 0.73 h⋅mg/L), as normalized to a 100 mg dose, were significantly lower compared with those of non-obese patients. No significant differences were observed regarding the free plasma concentration, as determined by ultrafiltration, or the corresponding AUC(8h) (fAUC(8h,plasma)). Concentrations in interstitial fluid (ISF) of subcutaneous tissue were lower than the free plasma concentrations in both groups, and they were lower in obese compared to non-obese patients: the AUC(8h) in ISF (AUC(8h,ISF)) was 0.51 ± 0.22 h⋅mg/L in obese and 0.79 ± 0.23 h⋅mg/L in non-obese patients, resulting in a relative tissue drug exposure (AUC(8h,ISF)/fAUC(8h,plasma)) of 0.38 ± 0.19 and 0.63 ± 0.24, respectively. CONCLUSION: Following a single dose of tigecycline, concentrations in the ISF of subcutaneous adipose tissue are decreased in heavily obese subjects, calling for an increased loading dose. EU CLINICAL TRIALS REGISTRATION NUMBER: EudraCT No. 2012-004383-22. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13318-022-00789-2. Springer International Publishing 2022-08-09 2022 /pmc/articles/PMC9399032/ /pubmed/35945479 http://dx.doi.org/10.1007/s13318-022-00789-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Short Communication
Dorn, Christoph
Petroff, David
Kratzer, Alexander
Kees, Frieder
Kloft, Charlotte
Zeitlinger, Markus
Wrigge, Hermann
Simon, Philipp
Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis
title Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis
title_full Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis
title_fullStr Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis
title_full_unstemmed Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis
title_short Tigecycline Soft Tissue Penetration in Obese and Non-obese Surgical Patients Determined by Using In Vivo Microdialysis
title_sort tigecycline soft tissue penetration in obese and non-obese surgical patients determined by using in vivo microdialysis
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399032/
https://www.ncbi.nlm.nih.gov/pubmed/35945479
http://dx.doi.org/10.1007/s13318-022-00789-2
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