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JAC Advance Access originally published online on October 24, 2008
Journal of Antimicrobial Chemotherapy 2009 63(1):167-169; doi:10.1093/jac/dkn442
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Biliary penetration and pharmacodynamic exposure of linezolid in liver transplant patients

Federico Pea1,*, Pierluigi Viale2, Manuela Lugano3, Umberto Baccarani4, Federica Pavan1, Marcello Tavio2, Gian Luigi Adani4, Giorgio Della Rocca3 and Mario Furlanut1

1 Institute of Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy 2 Clinic of Infectious Diseases, Department of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy 3 Department of Anaesthesiology and Intensive Care, University of Udine, Udine, Italy 4 Department of Surgery and Transplantation, Medical School, University of Udine, Udine, Italy

Received 22 July 2008; returned 2 September 2008; revised 22 September 2008; accepted 25 September 2008

* Corresponding author. Tel/Fax: +39-0432-559833; E-mail: pea.federico{at}aoud.sanita.fvg.it

Objectives: The aim of the study was to assess the biliary penetration of linezolid and the probabilities of attaining optimal pharmacodynamic exposure against vancomycin-resistant enterococci (VRE) in the bile of liver transplant (LTx) patients who received linezolid for the treatment of multidrug-resistant Gram-positive hospital infections.

Methods: After at least 2 days of standard 600 mg twice-daily therapy, simultaneous bile and blood samples for linezolid assay were collected from six LTx patients just prior to drug administration to determine trough concentrations (Cmin) at steady-state in both sites. Linezolid concentrations in plasma and in bile were analysed by means of HPLC. Biliary penetration of linezolid was calculated as the ratio between Cmin in bile and in plasma. Optimal theoretical pharmacodynamic exposure of linezolid against VRE in bile was defined as biliary Cmin > MIC90.

Results: Cmin of linezolid in bile achieved very high values at steady-state, which were significantly higher than in plasma (median of 21.77 versus 8.08 mg/L, P = 0.021). The very high biliary penetration of linezolid (median value of 1.93; range 1.31–4.83) enabled achievement of optimal theoretical pharmacodynamic exposure against VRE in bile (Cmin > 2 mg/L) on all of the occasions.

Conclusions: These preliminary data suggest a potential role for linezolid in the treatment of cholangitis due to VRE in LTx patients. Obviously, further confirmatory data assessing also the AUC/MIC ratio of linezolid in bile are needed.

Keywords: bile , VRE , pharmacokinetics , trough concentration , cholangitis


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