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JAC Advance Access originally published online on September 6, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):1074-1079; doi:10.1093/jac/dkm306
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© The Author 2007. 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

Disposition of linezolid in the isolated rat lung after systemic and pulmonary drug delivery

María José de Jesús Valle, Nora Salamanca Uranga, Francisco Gónzalez López, Alfonso Domínguez-Gil Hurlé and Amparo Sánchez Navarro*

Pharmacy Department, University of Salamanca, Licenciado Méndez Nieto, s/n 37007, Salamanca, Spain

Received 4 April 2007; returned 23 June 2007; revised 9 July 2007; accepted 22 July 2007

* Corresponding author. Tel: +34-923-294536; Fax: +34-923-294515; E-mail: asn{at}usal.es

Objectives: To characterize the distribution of linezolid in lung when it accesses this organ from the systemic circulation and when administered through the pulmonary route and to evaluate the influence of the ‘respiratory mode’ in the pulmonary distribution for both routes.

Methods: The study was conducted with 24 Wistar rats divided into four groups treated with linezolid under different experimental conditions. After the animals had been subjected to a tracheotomy followed by mechanical ventilation, the lungs were isolated. After a 5 min stabilization period, the antibiotic was administered through the systemic or the pulmonary route and samples of efferent fluid (EF) were collected using a previously programmed fraction collector. Samples of bronchoalveolar fluid (BALF) and of lung tissue were also taken at the end of each experiment. The concentrations of linezolid in the samples were determined using an HPLC technique with UV detection.

Results: The administration of linezolid through the inhalatory route significantly increased the levels of the drug in lung tissue and BALF with lung tissue/EF partition coefficients of 8.33 ± 2.51 as compared with 1.90 ± 0.78 for systemic administration. Also, the decrease in respiratory rate together with the increase in tidal volume favoured the process of linezolid distribution in pulmonary tissues and fluids.

Conclusions: Administration through the pulmonary route affords and excellent method for passively vectoring linezolid to the pulmonary fluids and tissues and the respiratory mode seems to affect the disposition of the antibiotic in this tissue for both administration routes.

Keywords: pulmonary distribution , pulmonary delivery , respiratory patterns


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