Assessment of pulmonary function and serum substance levels in newborn and juvenile rats.
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.
Lewin
Geertje
G
Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625 Hannover, Germany. geertje.lewin@item.fraunhofer.de
Hoymann
Heinz-Gerd
HG
Fuhst
Rainer
R
Berger-Preiss
Edith
E
Pohlmann
Gerhard
G
Buschmann
Jochen
J
D000280:Administration, Inhalation; D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D008168:Lung / Q000187:drug effects*; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood; D010993:Plethysmography, Whole Body; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood
D004364:Pharmaceutical Preparations; D014700:Verapamil