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Eur Respir J 2004; 24:150-156
Copyright ©ERS Journals Ltd 2004

Comparison of 99mTc-DTPA and urea for measuring cefepime concentrations in epithelial lining fluid

S. Bayat1, K. Louchahi2, B. Verdière3, D. Anglade1, A. Rahoui3, P-M. Sorin1, M. Tod2, O. Petitjean2, F. Fraisse3 and F.A. Grimbert1

1 Techniques d'Imagerie, de Modélisation et de Cognition, Centre National de Recherche Scientifique, Unité Mixte de Recherche 5525, Dépt de Physiologie, Université Joseph Fourier, Faculté de Médecine de Grenoble, La Tronche, 2 Dépt de Pharmacotoxicologie, Hôpital Avicenne, Bobigny, and 3 Service de Réanimation, Centre Hospitalier Général de Saint-Denis, Saint-Denis, France

CORRESPONDENCE: S. Bayat, European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble, France. Fax: 33 476882885. E-mail: bayat@esrf.fr

Keywords: Acute respiratory distress syndrome, antibiotics, blood/air barrier, bronchoalveolar lavage fluid, pulmonary alveoli

Received: September 18, 2003
Accepted February 5, 2004

This study was funded by grants from the Bristol-Myers-Squibb Company (New York, NY, USA) and the French Cystic Fibrosis Association (Paris, France) (AFLM, RC99008).

The efficacy of antimicrobial agents against pulmonary infections depends on their local concentrations in the lung. The aims of the present study were to: 1) compare technetium-99m diethylenetriaminepenta-acetic acid (99mTc-DTPA) and urea as markers of epithelial lining fluid (ELF) dilution for measuring ELF concentrations of pharmaceuticals; 2) quantify ELF cefepime concentrations in normal and injured lung; and 3) measure the increase in permeability to cefepime following oleic acid-induced acute lung injury.

A modified bronchoalveolar lavage technique, based on equilibration of infused 99mTc-DTPA, was used to measure ELF volume. Cefepime was administered intravenously at steady plasma levels. Six serial bronchoalveolar lavages were performed 5 h after the beginning of infusion.

ELF to plasma cefepime concentration ratios were 95±17 and 100±14.5% in normal and injured lung respectively. When urea was used as marker, cefepime concentration ratios were underestimated at 16.4±2.7 and 73.9±8.4% respectively. Cefepime blood/airspace clearance increased from 3.8±0.7 µL·min–1 in controls to 39.8±4.9 µL·min–1 in acute lung injury.

It was concluded that: 1) cefepime concentrations in epithelial lining fluid were in equilibrium with those in plasma in both normal and injured lung after 5 h at steady plasma concentrations; 2) epithelial lining fluid cefepime concentration by the urea method was much less underestimated in injured versus normal lung; and 3) acute lung injury induces a 10-fold elevation of cefepime blood/airspace clearance.






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