Metabolism of amiodarone following intratracheal instillation in hamsters

Intratracheal instillation of the antiarrhythmic drug amiodarone (AD) in hamsters is an established animal model of AD-induced pulmonary fibrosis. A metabolite of AD, desethylamiodarone (dAD), has also been shown to produce pulmonary fibrosis in this model. It was previously reported that following intratracheal instillation of AD in hamsters, metabolite could not be detected in lung tissue. However, in studies in our laboratory dAD was detected following instillation of AD. The goal of the present study was to monitor the distribution of AD and dAD to lung and liver within 1 h of AD instillation and to investigate the site of AD metabolism. Both AD and dAD were detected in the lung and liver within 5 min of AD instillation; lung and liver concentrations of AD and dAD were also quantified at 30 and 60 min following AD instillation. Incubation of lung and liver microsomes with AD showed that the liver is a probable site of AD metabolism following the intratracheal administration of AD to hamsters.