Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome
Matthias Otto,
Jörg Krebs,
Peter Welker,
René Holm,
Manfred Thiel,
Luciano Gattinoni,
Michael Quintel,
Charalambos Tsagogiorgas
Affiliations
Matthias Otto
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany
Jörg Krebs
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany
Peter Welker
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany
René Holm
Drug Product Development, Janssen Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium
Manfred Thiel
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany
Luciano Gattinoni
Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
Michael Quintel
Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
Charalambos Tsagogiorgas
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany
Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.
