Comparison of inhalation toxicity studies of gentamicin in rats and dogs

Autor:	Heather Conway, Henry G Wall, Jacob D. McDonald, Matthew D. Reed, Ronald K. Wolff, Kelly J. Dix, Rodney A. Miller
Rok vydání:	2013
Předmět:	Male medicine.medical_specialty Health Toxicology and Mutagenesis medicine.medical_treatment Toxicology Necrosis Dogs Species Specificity Internal medicine Administration Inhalation Toxicity Tests medicine Animals Respiratory system Saline Lung Inhalation business.industry Anti-Bacterial Agents Rats medicine.anatomical_structure Endocrinology Kidney Tubules Anesthesia Toxicity Gentamicin Histopathology Female Gentamicins business Respiratory tract medicine.drug
Zdroj:	Inhalation toxicology. 25(13)
ISSN:	1091-7691
Popis:	Nebulized gentamicin solution was administered to rats (nose-only) and dogs (face mask) for 14 days with a 14-day recovery period. Control groups of each were exposed to saline aerosols. Mean estimated inhaled lung doses of gentamicin were 39, 123 and 245 mg/kg for rats (deposited doses 6, 17 and 34 mg/kg) over 30, 90 and 180 min, respectively. Since dogs do not tolerate exposures as long as rats, inhaled lung doses were limited to 7, 14 and 41 mg/kg (deposited doses of 1, 3 and 8 mg/kg) over 15, 30 and 60 min. Comparable doses were achieved at the low dose for rats and high dose for dogs. Serum AUCs (14 ± 2 µg/mL h (mean ± SD) at 6 mg/kg in rats and 11 ± 7 µg/mL h at 8 mg/kg in dogs) showed comparable exposure between the two, implying similar absorbed doses and confirming similar deposited lung doses. Rat exposures resulted in dose-related lung pathology (including low dose) manifested as upper respiratory tract irritant reactions with alveolar histiocytosis, inflammation, airway epithelial metaplasia and lymphomegaly in lung tissue. This was associated with high lung tissue gentamicin levels 24 h post-dose on Day 14 (375 ± 33 µg/g at deposited dose of 6 mg/kg). Dose-related kidney tubular necrosis (a well-known toxicity of parenteral gentamicin) was observed, but no test-article related effects on lung histopathology in dogs (even at highest deposited dose of 8 mg/kg) and low levels of lung tissue gentamicin (42 ± 11 µg/g) 24 h post-dose on Day 14.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5810f83a07157d1bc42c4c6934fbf03 https://pubmed.ncbi.nlm.nih.gov/24255949 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.