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AAC Accepts, published online ahead of print on 30 June 2008
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Antimicrob. Agents Chemother. doi:10.1128/AAC.00242-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Lung Microdialysis Study of Levofloxacin in Rats following Intravenous Infusion at Steady-State

Sandrine Marchand, Denis Frasca, Claire Dahyot-Fizelier, Céline Breheret, Olivier Mimoz, and William Couet*

Inserm, ERI-23, 40 Avenue du recteur Pineau, Poitiers, France; Université de Poitiers, UFR Médecine-Pharmacie, 6 rue de la Milétrie, Poitiers, France; CHU Poitiers, 2 Rue de la Milétrie, Poitiers, France

* To whom correspondence should be addressed. Email: william.couet{at}univ-poitiers.fr.


   Abstract

Lung microdialysis has been used in rats to investigate antibiotics distribution after single dose administration. However conducting such experiments after intravenous infusion at steady-state would constitute a more convenient alternative which is now evaluated, using levofloxacin (LVX) as a test compound. Microdialysis probes were inserted in blood and muscle, used as a comparator, between 9:00 pm and 11:00 am. Levofloxacin (LVX) intravenous infusion was then started and maintained until the end of experiment at a rate of 1.0 mg.h-1. Lung microdialysis probe were inserted on the morning of next day. Rats were maintained anesthetized during dialysates collection. In vivo probes recoveries were estimated by the retrodialysis by calibrator method with cirpofloxacin (CIP) as a calibrator. LVX and CIP were analysed in dialysates by high-performance liquid chromatography (HPLC). Steady-state unbound tissue to blood concentrations ratios were respectively equal to 1.00 ± 0.15 in muscle and 1.06 ± 0.40 in lung, suggesting passive tissue distribution of LVX. Although providing no information on the rate of distribution, microdialysis investigations following drug infusion at steady-state appear as an interesting approach for the characterization of antibiotics lung distribution in rats.







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