Development of a new aerosol delivery system for systemic pulmonary delivery in anaesthetized and orotracheal intubated rats

Over the last decade, the systemic absorption of a broad range of therapeut ics after pulmonary application has been demonstrated ill animals as well a s in humans. The most common method used in the laboratory is the intratrac heal instillation of drugs in solution. This method, is, however, unsatisfa ctory, because of discrepancies in particle distribution, clearance, kind o f injury and bioavailability between instillation and inhalative applicatio n. On the other hand, a precise determination of the amount of drug applied by aerosol, and of the aerosol volume retained within the lungs is rather difficult, and is not possible for use with small animals such as mice or r ats. We describe a system which allows the delivery of aerosols directly in to the animal's lungs, and calculation of the amount of drug retained in th e lungs. Our system was tested in vitro and in vivo and was shown to allow precise and efficient pharmacokinetic and toxicological studies to be carri ed out.