title: Resistance of the hamster to amiodarone-induced pulmonary toxicity following repeated intraperitoneal administration.
abstract: Amiodarone is an effective antidysrhythmic agent, restricted in use by the development of pulmonary toxicity. Several in vivo animal models have been used to study amiodarone-induced pulmonary toxicity. Intratracheal administration of amiodarone to the hamster has been used as a model for the critical amiodarone-induced pulmonary fibrosis (AIPF). In order to investigate the cellular mechanism of human AIPF, which occurs following oral or intravenous administration, an animal model of AIPF resulting from systemic administration of the drug would appear to be preferable. We have evaluated pulmonary toxicity following repeated intraperitoneal amiodarone administration to the hamster. Intraperitoneal treatment of hamsters for 1, 4, or 7 weeks with amiodarone (100 mg/kg/day) did not lead to pulmonary toxicity based on wet lung weight, hydroxyproline content, or histological examination. Furthermore, when comparing 1- and 7-week treatment groups, there was no pulmonary accumulation of either amiodarone or desethylamiodarone beyond levels found at 1 week. Therefore, failure to develop pulmonary toxicity may be due to an inability to accumulate sufficient amiodarone and/or desethylamiodarone. Intratracheal administration of amiodarone to rodents remains the only in vivo animal model for studying the mechanism(s) of AIPF.
authors.affiliation: Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
authors.forename: R G
authors.initials: RG
authors.lastname: Leeder
authors.forename: C D
authors.initials: CD
authors.lastname: Evans
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
authors.forename: T E
authors.initials: TE
authors.lastname: Massey
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004195:Disease Models, Animal; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: C036116:desethylamiodarone; D000638:Amiodarone; D006909:Hydroxyproline