BACKGROUND: In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated @entity805 vaccine was administered to @entity5434 ( @entity5434 ) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions. METHODS: Drug delivery varies with breathing parameters. Therefore we determined macaque breathing patterns (tidal volume, breathing frequency, and inspiratory to expiratory (I:E) ratio) across a range of 3.3-6.5   kg body weight, using a pediatric pneumotachometer interfaced either with an endotracheal tube or a facemask. Subsequently, these breathing patterns were reproduced using a breathing simulator attached to a filter to collect the inhaled dose. @entity3045 was nebulized using a vibrating mesh nebulizer and the percentage inhaled dose was determined by extraction of drug from the filter and subsequent quantification. RESULTS: Tidal volumes ranged from 24 to 46   mL, breathing frequencies from 19 to 31 breaths per minute and I:E ratios from 0.7 to 1.6. A small pediatric resuscitation mask was identified as the best fitting interface between animal and pneumotachometer. The average efficiency of inhaled dose delivery was 32.1% (standard deviation 7.5, range 24%-48%), with variation in tidal volumes as the most important determinant. CONCLUSIONS: Studies in non- @entity1 primates aimed at comparing aerosol delivery with other routes of administration should take both the inter-subject variation and relatively low efficiency of delivery to these low body weight mammals into account.

Optimization and Dose Estimation of Aerosol Delivery to Non- XXXX Primates.

@entity1 :: ('9606', 'Species') :: ['human'] @entity3045 :: ('MESH:D000420', 'Chemical') :: ['Albuterol'] @entity805 :: ('11234', 'Species') :: ['measles virus'] @entity5434 :: ('9541', 'Species') :: ['Macaca fascicularis', 'cynomolgus monkeys']
@entity1 :: (9606,Species) :: ['Human']
