Otto Matthias, Krebs Jörg, Welker Peter, Holm René, Thiel Manfred, Gattinoni Luciano, Quintel Michael, Tsagogiorgas Charalambos
Department of Anaesthesiology and Critical Care Medicine, University Hospital Mannheim, Faculty of Medicine, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68165 Mannheim, Germany.
Drug Product Development, Janssen Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium.
Pharmaceutics. 2021 Mar 23;13(3):431. doi: 10.3390/pharmaceutics13030431.
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.
迄今为止，急性呼吸窘迫综合征（ARDS）患者的雾化治疗未能改善患者的预后。这可能是因为传统气雾剂无法到达肺低垂区域。由于其物理化学性质，半氟化烷烃（SFAs）可以解决这个问题。诱导ARDS后，将26头猪随机分为三组：（1）对照组（假手术组），（2）全氟己基辛烷（F6H8）组，和（3）F6H8-布洛芬组。使用雾化导管，（2）组接受1 mL/kg F6H8，而（3）组接受1 mL/kg F6H8与6 mg/mL布洛芬的混合物。测量布洛芬的血浆和肺组织浓度、支气管肺泡灌洗（BAL）液中TNF-α、IL-8和IL-6的浓度以及肺力学。布洛芬浓度在右肺低垂部位均匀分布。药代动力学数据表明布洛芬存在全身吸收，证明其可穿过肺泡-毛细血管膜。与对照组（1）相比，（2）组和（3）组中TNF-α浓度显著降低。IL-8和IL-6浓度以及肺力学方面无显著差异。F6H8气雾剂似乎是将药物输送到ARDS肺低垂区域的合适载体，且对肺力学无负面影响。
