title: Developments and strategies for inhaled antibiotic drugs in tuberculosis therapy: a critical evaluation.
abstract: Inhaled antibiotics have been a valuable tool in treating pulmonary infections in cystic fibrosis patients for decades, and the pulmonary route is now becoming increasingly interesting for other infectious diseases like tuberculosis too. Especially with multidrug and extensively drug-resistant tuberculosis emerging, great effort is put into the improvement of pulmonary antibiotic administration to fight this global threat. Several reviews have been written on inhalable antibiotics, giving clear overviews of the compounds of interest. Furthermore, various formulation studies and administration strategies are on-going with these compounds. What is often missing is a critical evaluation of these developments. Several risks may be involved varying from obtaining insufficient local drug concentrations to adverse side effects and unwanted changes in physiological processes from the excipients used. In this manuscript, the pros and cons and feasibility of recent advances in pulmonary antibiotic tuberculosis therapy are presented and critically evaluated. Furthermore, the advantages of dry powder inhalation over wet nebulisation for inhaled antibiotics in developing countries where prevalence of tuberculosis is highest are discussed. It has to be concluded that a greater effort in good inhaler development and more research in the physico-chemical properties of the compounds of interest are needed.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: m.hoppentocht@rug.nl.
authors.forename: M
authors.initials: M
authors.lastname: Hoppentocht
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Hagedoorn
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: de Boer
mesh_terms: D000280:Administration, Inhalation; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D055808:Drug Discovery; D058995:Dry Powder Inhalers; D006801:Humans; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000904:Antibiotics, Antitubercular
keywords: Antibiotics; Dry powder inhalers; Inhaled antibiotics; Pulmonary administration; Pulmonary infections; Tuberculosis