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

• Published in: The European respiratory journal Vol. 24; no. 1; pp. 150 - 156
• Main Authors: Bayat, S, Louchahi, K, Verdiere, B, Anglade, D, Rahoui, A, Sorin, P-M, Tod, M, Petitjean, O, Fraisse, F, Grimbert, F.A
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.07.2004; Maney
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Biological Availability; Biological Transport, Active; Bronchoalveolar Lavage Fluid - chemistry; Cefepime; Cephalosporins - pharmacokinetics; Cephalosporins - pharmacology; Disease Models, Animal; Dogs; Epithelium; Female; Infusions, Intravenous; Male; Medical sciences; Pneumology; Pneumonia - drug therapy; Radiopharmaceuticals - pharmacology; Sensitivity and Specificity; Technetium Tc 99m Pentetate; Urea; Acute respiratory distress syndrome; Urea; Cefepime; pulmonary alveoli; blood/air barrier; bronchoalveolar lavage fluid; Concentration; antibiotics; Comparative study; Pneumology
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.04.00106803

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 micro x min(-1) in controls to 39.8 +/- 4.9 microL x 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.