Challenges for Inhaled Drug Discovery and Development: Induced Alveolar Macrophage Responses

  • Publication Date :
  • Publication Type : Journal Article
  • Author(s) : Forbes B, O'Lone R, Allen PP, Cahn A, Clarke C, Collinge M, Dailey LA, Donnelly LE, Dybowski J, Hassall D, Hildebrand D
  • Journal Name : Advanced Drug Delivery Reviews

Advanced Drug Delivery Reviews. 2014;71C:15-33

Abstract: Alveolar macrophage (AM) responses are commonly induced in inhalation toxicology studies, typically being observed as an increase in number or a vacuolated ‘foamy’ morphology. Discriminating between adaptive AM responses and adverse events during nonclinical and clinical development is a major scientific challenge. When measuring and interpreting induced AM responses, an understanding of macrophage biology is essential; this includes ‘sub-types’ of AMs with different roles in health and disease and mechanisms of induction/resolution of AM responses to inhalation of pharmaceutical aerosols. In this context, emerging assay techniques, the utility of toxicokinetics and the requirement for new biomarkers are considered. Risk assessment for nonclinical toxicology findings and their translation to effects in humans is discussed from a scientific and regulatory perspective. At present, when apparently adaptive macrophage-only responses to inhaled investigational products are observed in nonclinical studies, this poses a challenge for risk assessment and an improved understanding of induced AM responses to inhaled pharmaceuticals is required.

To download an open-access PDF copy, click here.

Contact Us

Health and Environmental Sciences Institute (HESI)
Phone: +1-202-659-8404
Fax: +1-202-659-3859

740 15th Street NW, Suite 600
Washington, DC 20005

Stay Informed

Sign up for our monthly e-newsletter.