Related Experiment Video
Updated: Jun 12, 2026
A Minimally Invasive Method for Intratracheal Instillation of Drugs in Neonatal Rodents to Treat Lung Disease
Published on: August 4, 2021
Assessment of pulmonary function and serum substance levels in newborn and juvenile rats
Geertje Lewin1, Heinz-Gerd Hoymann, Rainer Fuhst
1Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625 Hannover, Germany. geertje.lewin@item.fraunhofer.de
Insights
New inhalation and plethysmography methods assess juvenile rat lung function for pediatric drug safety. These techniques support human neonatal risk assessment and are suitable for regulatory studies.
Area of Science:
- Pharmacology and Toxicology
- Developmental Biology
- Respiratory Physiology
Background:
- Regulatory authorities increasingly require pediatric drug approval studies.
- The developing lung is a critical target for juvenile toxicity assessments.
- Physiological differences necessitate modified methods for assessing pulmonary function in juvenile animal models.
Purpose of the Study:
- To establish feasible methods for assessing pulmonary function in juvenile rats.
- To provide basic respiratory parameter data for neonatal risk assessment.
- To validate animal models for regulatory pediatric drug safety studies.
Main Methods:
- Noninvasive nose-only inhalation exposure of juvenile Wistar (WU) rats (postnatal days 4-21) with verapamil HCl.
- Noninvasive plethysmographic measurements in conscious juvenile Wistar (WU) rats (postnatal days 2-50).
Main Results:
- The developed methods were feasible for juvenile rats.
- Inhalation exposure and plethysmography did not interfere with normal animal growth and development.
- The techniques provided new insights for human neonatal risk assessment.
Conclusions:
- Modified inhalation and plethysmography methods are suitable for juvenile toxicity studies.
- These techniques support regulatory requirements for pediatric drug approval.
- The validated animal models aid in human neonatal risk assessment.
Abstract:
In the context of pharmaceutical development today, studies for pediatric drug approval are requested more and more often by the regulatory authorities. The developing lung represents a potential target in juvenile toxicity studies. Due to physiological differences in prenatal and postnatal development between humans and standard animal models, experimental methods have to be modified to assess pulmonary function, and basic data on respiratory parameters need to be provided. Daily nose-only inhalation exposure from postnatal days 4 to 21 using a model substance (verapamil HCl) and plethysmographic measurements between postnatal days 2 and 50 were performed noninvasively in conscious juvenile Wistar (WU) rats. The methods proved to be feasible and did not interfere with normal growth and development of the animals. Both techniques therefore permit new insights to support human neonatal risk assessment and therefore these animal models are suitable for regulatory studies.
