title: Symposium Summary: "Breathe In, Breathe Out, Its Easy: What You Need to Know About Developing Inhaled Drugs".
abstract: Developing inhaled drugs requires knowledge of lung anatomy, cell biology, respiratory physiology, particle physics, and some plumbing. Although dose makes the poison, in the context of an inhaled drug, the "dose" is not easily defined. This lack of clarity around dose poses issues and challenges in the design of inhalation toxicology programs. To better understand dose, the influence of ventilation is discussed as are the perturbations in pulmonary function observed with inhalation exposure that can affect dose. Methods for determining inhaled drug deposition to arrive at an estimate of lung dose are examined. Equally important to understanding dose are the techniques used to deliver aerosols to animals. With a better understanding of dose and inhalation exposure, species-specific histopathologic lesions, both common background and toxicologically significant lesions, are reviewed. Finally, insight into how regulators synthesize and evaluate these complex findings to assess clinical safety risks is presented.
authors: Tepper Nonclinical Consulting, San Carlos, CA, USA teppertox@gmail.com.
authors: Jeffrey S
authors: JS
authors: Tepper
authors: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors: Philip J
authors: PJ
authors: Kuehl
authors: Group Director, Aerosol Technology, Huntingdon Life Sciences, Somerset, NJ, USA.
authors: Stuart
authors: S
authors: Cracknell
authors: Executive Vice President and CSO, Seventh Wave Laboratories, LLC, Maryland Heights, MO, USA.
authors: Kristen J
authors: KJ
authors: Nikula
authors: US Food and Drug Administration, Silver Spring, MD, USA.
authors: Luqi
authors: L
authors: Pei
authors: Preclinical Development, Aradigm Corp, Hayward, CA, USA.
authors: James D
authors: JD
authors: Blanchard
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006801:Humans; D007880:Legislation, Drug; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000033:anatomy & histology / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations
keywords: allometry; deposition; dosimetry; inhalation toxicology; lung imaging; lung pathology; orally inhaled products; pharmacokinetics; pulmonary function; respiratory product development; safety evaluation; safety margins