Linked Life Data

19230021

Source:http://linkedlifedata.com/resource/pubmed/id/19230021

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-10-1
pubmed:abstractText
Inhaled corticosteroids (ICSs) are often prescribed as the first line therapy for pulmonary diseases such as asthma. The biggest concern of using steroid therapy is the systemic side effects at high dose. To reduce the side effects, the pharmaceutical industry has been putting effort to generate new drugs with maximized topical efficacy. One of the key challenges is to differentiate efficacy from local versus systemic contribution in preclinical animal models. Fluticasone with various formulations was used as a model compound to explore the possibilities to demonstrate lung targeted efficacy by intratracheally instillation in the lipopolysaccharide induced inflammation rat model. Fluticasone formulations contained various surfactant concentrations and particle sizes to achieve lung retention and lower systemic exposure. Neutrophil infiltration in broncoalveolar lavage fluid and cytokine production in whole blood were measured to assess pulmonary efficacy versus systemic efficacy. PK/PD characterization of fluticasone with various formulations in the rat inflammation model provided an integrated approach in preclinical to evaluate lung targeted efficacy for ICS. Our study concluded that the combination of the rat LPS model and fluticasone is not suitable to use for establishing potency and dose requirement for new drug candidate designed for topical only efficacy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-6017
pubmed:author
pubmed:copyrightInfo
(c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association
pubmed:issnType
Electronic
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4354-64
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Pharmacokinetic and pharmacodynamic evaluation of the suitability of using fluticasone and an acute rat lung inflammation model to differentiate lung versus systemic efficacy.
pubmed:affiliation
Global Research and Development, Pharmaceutical Research and Development, St. Louis Laboratories, Pfizer Inc., 700 Chesterfield Parkway N. T2F, Chesterfield, Missouri, USA. po-chang.chiang@pfizer.com
pubmed:publicationType
Journal Article, Evaluation Studies