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

URN to cite this document:: urn:nbn:de:bvb:355-epub-527959
DOI to cite this document:: 10.5283/epub.52795

Dorn, Christoph

; Petroff, David ; Kratzer, Alexander ; Kees, Frieder ; Kloft, Charlotte ; Zeitlinger, Markus

; Wrigge, Hermann ; Simon, Philipp

License: Creative Commons Attribution Non-commercial 4.0
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Date of publication of this fulltext: 25 Aug 2022 04:27

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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.

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