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Characterization of colistin tissue pharmacokinetics by microdialysis

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HAL Id: inserm-00732898

https://www.hal.inserm.fr/inserm-00732898

Submitted on 17 Sep 2012

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Characterization of colistin tissue pharmacokinetics by

microdialysis

Peter Matzneller, William Couet, Patrice Gobin, Markus Müller, Markus

Zeitlinger

To cite this version:

Peter Matzneller, William Couet, Patrice Gobin, Markus Müller, Markus Zeitlinger. Characterization

of colistin tissue pharmacokinetics by microdialysis. BMC Pharmacology and Toxicology, BioMed

Central, 2012, 13 (Suppl 1), pp.A74. �10.1186/2050-6511-13-S1-A74�. �inserm-00732898�

(2)

M E E T I N G A B S T R A C T

Open Access

Characterization of colistin tissue

pharmacokinetics by microdialysis

Peter Matzneller

1

, William Couet

2

, Patrice Gobin

2

, Markus Müller

1

, Markus Zeitlinger

1*

From

18th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint meeting with the

Croatian, Serbian and Slovenian Pharmacological Societies.

Graz, Austria. 20-21 September 2012

Background

Colistin is an important antimicrobial treatment option against multidrug-resistant Gram-negative bacteria. How-ever, colistin is a large and chemically complex molecule and information on its ability to penetrate into tissues remains sparse. Thus, the present work investigated the ability of microdialysis (µD) to assess pharmacokinetics (PK) of colistin in the interstitium of soft tissues, i.e. at a potential site of infection.

Methods

In vitro:Colistin recovery for linear CMA 66 µD probes with a molecular weight cut-off of 100 kDa was assessed through forward and reverse µD for different colistin con-centrations. In vivo: Three male healthy volunteers received a single intravenous dose of 2.5 million interna-tional units of the inactive prodrug colistin methanesulfo-nate. Colistin concentrations in plasma and in µD samples obtained from two probes inserted into subcutaneous adi-pose tissue of the thigh were determined. Retrodialysis was used for probe calibration. In both settings, µD was performed with and without addition of albumin to perfu-sion solutions and colistin was quantified by liquid chro-matography/tandem mass spectrometry (LC-MS/MS).

Results

In vitro, colistin recovery was constant over time and showed mean recovery values of 52 ± 3 and 71 ± 8% for forward and reverse µD, respectively. In vivo, recovery of colistin was 43 ± 15%. In both settings, colistin recovery was not improved by addition of albumin to µD perfusion solutions. Due to small volumes, reliable quantification of

colistin was not possible in some µD samples, yet maxi-mum concentrations in adipose tissue were relatively high (0.76 ± 0.21 µg/mL) compared with those in plasma (1.2 ± 0.43 µg/mL) attesting for extra-vascular distribution.

Conclusions

The present data demonstrate the feasibility of µD for evaluation of colistin tissue pharmacokinetics and show opportunities for optimization of experimental setting.

Author details

1

Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.2Inserm ERI-23, Faculty of Medicine, University of Poitiers,

86022 Poitiers Cedex, France. Published: 17 September 2012

doi:10.1186/2050-6511-13-S1-A74

Cite this article as:Matzneller et al.: Characterization of colistin tissue pharmacokinetics by microdialysis. BMC Pharmacology and Toxicology 2012 13(Suppl 1):A74.

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Submit your manuscript at www.biomedcentral.com/submit * Correspondence: markus.zeitlinger@meduniwien.ac.at

1

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

Full list of author information is available at the end of the article

Matzneller et al. BMC Pharmacology and Toxicology 2012, 13(Suppl 1):A74 http://www.biomedcentral.com/2050-6511/13/S1/A74

© 2012 Matzneller et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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