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Penetration of Ertapenem Into Different Pulmonary Compartments of Patients Undergoing Lung Surgery

From the Department of Pulmonary and Critical Care Medicine, University Otto-von-Guericke, Magdeburg, Germany, and the Department of Pulmonary Medicine, Medical School Hannover, Germany (Dr Burkhardt, Dr Welte); the Department of Clinical Pharmacology, University Rostock, Germany (Dr Majcher-Peszynska, Dr Mundkowski, Dr Drewelow); the Department of Clinical Chemistry and Pathobiochemistry, Free University Berlin, Germany (Dr Borner); and the College of Pharmacy, Department of Pharmaceutics, University of Florida, Gainesville (Dr Burkhardt, Dr Derendorf).

Ertapenem is approved for the treatment of community-acquired pneumonia (CAP), but its in vivo penetration into lung tissue (LT), epithelial lining fluid (ELF), and alveolar cells (AC) is unknown. Fifteen patients undergoing thoracotomy were treated with 1 g intravenously for perioperative prophylaxis. Bronchoalveolar lavage was performed 1, 3, and 5 hours after ertapenem infusion. Normal LT was sampled at the time of lung extraction. Blood was collected before and at different time points up to 24 hours after infusion. Mean concentrations of ertapenem in plasma, ELF, and AC were at 1.0 hour, 63.1, 4.06, 0.004 mg/L; at 3.0 hours, 39.7, 2.59, 0.003 mg/L; and at 5.0 hours, 27.2, 2.83, 0.007 mg/L. Mean (range) concentration in LT was 7.60 (2.5-19.4) mg/kg tissue 1.5 to 4.5 hours after infusion. In plasma, ertapenem exhibited a C_max of 94.7 ± 23.3 mg/L and an AUC_0-last of 501.1 ± 266.3 mg•h/L. These results, combined with the reported (MIC)₉₀ of most CAP bacteria, support the previously observed clinical efficacy of ertapenem in the treatment of CAP.

Key Words: Ertapenem • pharmacokinetics • plasma • lung tissue • ELF • alveolar cells • CAP

Address for reprints: Olaf Burkhardt, MD, College of Pharmacy, Department of Pharmaceutics, University of Florida, PO Box 100494, Gainesville, FL 32610.

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