Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?
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Laboratory for Biological Characterisation of Advanced Materials (LBCAM), Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College, The University of Dublin, Dublin D8, Ireland
2
AMBER Centre, CRANN Institute, Trinity College, The University of Dublin, Dublin D2, Ireland
*
Author to whom correspondence should be addressed.
Animals 2020, 10(8), 1259; https://doi.org/10.3390/ani10081259
Received: 30 June 2020
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Revised: 20 July 2020
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Accepted: 21 July 2020
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Published: 24 July 2020
(This article belongs to the Special Issue Are Animal Models Needed to Discover, Develop and Test Pharmaceutical Drugs for Humans in the 21st Century?)
Simple Summary
This commentary focuses on the methods currently available to test the efficacy and safety of new orally inhaled drugs for the treatment of uncurable respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer, prior to entering human experimentation. The key question that the authors try to address in this manuscript is whether there is value in using and refining current animal models for this pre-clinical testing, or whether these should be relinquished in favor of new, more human-relevant non-animal methods.
Respiratory diseases constitute a huge burden in our society, and the global respiratory drug market currently grows at an annual rate between 4% and 6%. Inhalation is the preferred administration method for treating respiratory diseases, as it: (i) delivers the drug directly at the site of action, resulting in a rapid onset; (ii) is painless, thus improving patients’ compliance; and (iii) avoids first-pass metabolism reducing systemic side effects. Inhalation occurs through the mouth, with the drug generally exerting its therapeutic action in the lungs. In the most recent years, orally inhaled drugs (OIDs) have found application also in the treatment of systemic diseases. OIDs development, however, currently suffers of an overall attrition rate of around 70%, meaning that seven out of 10 new drug candidates fail to reach the clinic. Our commentary focuses on the reasons behind the poor OIDs translation into clinical products for the treatment of respiratory and systemic diseases, with particular emphasis on the parameters affecting the predictive value of animal preclinical tests. We then review the current advances in overcoming the limitation of animal animal-based studies through the development and adoption of in vitro, cell-based new approach methodologies (NAMs).
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Keywords:
respiratory diseases; inhalation; preclinical studies; drug development; non-animal methods
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MDPI and ACS Style
Movia, D.; Prina-Mello, A. Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models? Animals 2020, 10, 1259. https://doi.org/10.3390/ani10081259
AMA Style
Movia D, Prina-Mello A. Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models? Animals. 2020; 10(8):1259. https://doi.org/10.3390/ani10081259
Chicago/Turabian StyleMovia, Dania, and Adriele Prina-Mello. 2020. "Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models?" Animals 10, no. 8: 1259. https://doi.org/10.3390/ani10081259
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