Pharmacokinetics of Inhaled Monodisperse Fluticasone Propionate

Summary

Asthma is most effectively treated by delivering inhaled drugs from an inhaler (puffer) directly into the lungs. Inhaled steroids are used in asthmatic patients to dampen down lung inflammation, which unchecked, can often lead to patient symptoms. Inhalers deliver a mist containing particles of lots of different sizes (like hairsprays). Medical puffers used by patients produce a 'coarse' mist of drug particles, which have the potential for side effects, as different sized particles will reach different parts of the airways and include; the mouth, the throat, the windpipe, and the bloodstream (all places we do not want the inhaled drug to go - and can give rise to important side effects)and, the lungs (where we do want the drug to 'deposit'). Our aim in this study is to test an inhaled steroid by giving it to subjects as a 'fine' mist containing drug particles of nearly all one size using a research nebuliser (a Spinning Top Aerosol Generator). We shall use small, intermediate and large drug particle mists. We aim to find out how much of the drug goes to the blood stream for each particle mist and compare it with the standard puffers used in routine clinical practice. We hope this study will provide information to the rationale that by improving the efficiency of drug delivery (by changing drug particle size) one may improve inhaled drug delivery and ultimately, clinical patient benefit. Healthy volunteers and asthmatic patients will be recruited at the Royal Brompton Hospital London. The study is funded by GlaxoSmithKline, Research \& Development, U.K.

Timeline

Start

2008-08

Primary completion

2011-07-03

Completion

2011-07-03

Publications

• Background Biddiscombe MF, Barnes PJ, Usmani OS. Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator. J Aerosol Med. 2006 Fall;19(3):245-53. doi: 10.1089/jam.2006.19.245.
• Background Usmani OS, Biddiscombe MF, Barnes PJ. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1497-504. doi: 10.1164/rccm.200410-1414OC. Epub 2005 Sep 28.
• Background Usmani OS, Biddiscombe MF, Nightingale JA, Underwood SR, Barnes PJ. Effects of bronchodilator particle size in asthmatic patients using monodisperse aerosols. J Appl Physiol (1985). 2003 Nov;95(5):2106-12. doi: 10.1152/japplphysiol.00525.2003. Epub 2003 Aug 1.
• Background Biddiscombe MF, Usmani OS, Barnes PJ. A system for the production and delivery of monodisperse salbutamol aerosols to the lungs. Int J Pharm. 2003 Mar 26;254(2):243-53. doi: 10.1016/s0378-5173(03)00032-2.

Drugs

Indications