Drug Regulatory Affairs, Pharmaceutical Institute, University Bonn, Bonn, Germany,
Adv Exp Med Biol. 2015;839:13-24. doi: 10.1007/5584_2014_50.
Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, and telithromycin) up to now are not administered by inhalation. The number of in vitro aerosol studies and in vivo inhalation studies is also sparse. We analyzed publications on preparation and administration of macrolide aerosols available in PUBMED focusing on recent publications. Studies with solutions and dry powder aerosols were published. Publications investigating physicochemical properties of aerosols demonstrated that macrolide aerosols may serve for inhalation and will achieve sufficient lung deposition and that the bitter taste can be masked. In vivo studies in rats demonstrated high concentrations and areas under the curve sufficient for antimicrobial treatment in alveolar macrophages and epithelial lining fluid without lung toxicity. The obtained data demonstrate the feasibility of macrolide inhalation which should be further investigated.
对于许多肺部疾病，如囊性纤维化（CF）、支气管扩张和慢性阻塞性肺疾病（COPD），系统抗生素治疗已得到确立，因为这些疾病反复发作的细菌感染会导致肺功能逐渐下降。在过去的几十年中，抗生素吸入疗法已被引入临床常规治疗，尤其是用于 CF 和支气管扩张的妥布霉素、多粘菌素和氨曲南。尽管由于其抗菌谱、抗炎和免疫调节特性，大环内酯类药物（如阿奇霉素、克拉霉素、红霉素和泰利霉素）在这些疾病的全身治疗中很重要，但直到现在它们还没有被吸入给药。关于大环内酯类药物气溶胶的体外气溶胶研究和体内吸入研究的数量也很少。我们分析了 PUBMED 上可获得的关于大环内酯类气溶胶制剂和给药的出版物，重点是近期的出版物。已发表了关于溶液和干粉气溶胶的研究。关于气溶胶物理化学性质的研究表明，大环内酯类气溶胶可用于吸入，将能达到足够的肺部沉积，并且苦味可以被掩盖。在大鼠体内研究中，肺泡巨噬细胞和上皮衬里液中获得了足够高的浓度和曲线下面积，可用于抗菌治疗，而没有肺部毒性。获得的数据证明了大环内酯类药物吸入的可行性，应进一步研究。
