dc.contributor.author | MacLoughlin, Ronan J. | |
dc.contributor.author | van Amerongen, Geert | |
dc.contributor.author | Fink, James B. | |
dc.contributor.author | Janssens, Hettie M. | |
dc.contributor.author | Duprex, W. Paul | |
dc.contributor.author | de Swart, Rik L. | |
dc.date.accessioned | 2018-09-20T16:15:20Z | |
dc.date.available | 2018-09-20T16:15:20Z | |
dc.date.issued | 2016-06-01 | |
dc.identifier.citation | MacLoughlin, Ronan J. van Amerongen, Geert; Fink, James B.; Janssens, Hettie M.; Duprex, W. Paul; de Swart, Rik L. (2016). Optimization and dose estimation of aerosol delivery to non-human primates. Journal of Aerosol Medicine and Pulmonary Drug Delivery 29 (3), 281-287 | |
dc.identifier.issn | 1941-2711,1941-2703 | |
dc.identifier.uri | http://hdl.handle.net/10379/12556 | |
dc.description.abstract | 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 measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) 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. Albuterol 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-human 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. | |
dc.publisher | Mary Ann Liebert Inc | |
dc.relation.ispartof | Journal of Aerosol Medicine and Pulmonary Drug Delivery | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | cynomolgus macaques | |
dc.subject | inhaled dose | |
dc.subject | non-human primates | |
dc.subject | tidal breathing | |
dc.subject | vibrating mesh nebulizer | |
dc.subject | pulmonary vaccine delivery | |
dc.subject | respiratory-function | |
dc.subject | young-children | |
dc.subject | deposition | |
dc.subject | challenges | |
dc.subject | facemasks | |
dc.subject | therapy | |
dc.subject | inhaler | |
dc.subject | infants | |
dc.subject | system | |
dc.title | Optimization and dose estimation of aerosol delivery to non-human primates | |
dc.type | Article | |
dc.identifier.doi | 10.1089/jamp.2015.1250 | |
dc.local.publishedsource | https://repub.eur.nl/pub/93835/REPUB_93835_AAM.pdf | |
nui.item.downloads | 0 | |