Linked Life Data

19933801

Source:http://linkedlifedata.com/resource/pubmed/id/19933801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-25
pubmed:abstractText
S-013420 (EDP-420) is a novel bicyclolide (bridged bicyclic macrolide) antibacterial currently under development for the treatment of respiratory tract infections. The objective of the present study was to determine the plasma and intrapulmonary pharmacokinetic parameters of orally administered S-013420 in healthy volunteers. Twenty-eight healthy Japanese male subjects who never smoked were randomly allocated to seven groups of four subjects each who underwent bronchoalveolar lavage (BAL) at different times after dosing (2, 4, 6, 8, 10, 12, or 24 h). Blood samples were also taken at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h after dosing. The S-013420 concentrations in plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs) were measured by using a combined high-performance liquid chromatography-mass spectrometric technique. A pharmacokinetic analysis of the plasma, ELF, and AM S-013420 concentration profiles was performed. S-013420 was rapidly absorbed in plasma, and the mean time to the maximum concentration in plasma was 2.27 h. S-013420 was rapidly distributed to the ELF and was slowly distributed to AMs. The areas under the concentration-time curves from time zero to 24 h (AUC0-24) for S-013420 were 20.3 times higher in ELF than in plasma and 244.6 times higher in AMs than in plasma. The mean maximum concentration in plasma was higher in ELF than in plasma and was much higher in AM than in plasma. Furthermore, pharmacodynamic calculations were done by using the AUC0-24/MIC90 ratio for common pneumonia pathogens (Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). The AUC0-24 for plasma/MIC90s for these four organisms were 41.8, 83.6, 1.3, and 20.9, respectively. The AUC0-24 for ELF/MIC90s were 849.6, 1,699.2, 26.6, and 424.8, respectively. Considering the good efficacy shown in a subsequent phase 2 study (S. Kohno, K. Yamaguchi, Y. Tanigawara, A. Watanabe, A. Aoki, Y. Niki, and J. Fujita, Abstr. 47th Intersci. Conf. Antimicrob. Agents Chemother., abstr. L-485), the good distribution of S-013420 in AMs and ELF observed in the present study is predictive of the good efficacy of S-013420 against respiratory pathogens.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-11850288, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-12435719, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-12775677, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-16224186, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-17846133, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-18201149, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-1963411, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-3512509, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-7709007, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-8807050, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-8891147, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-8913469, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-9109156, http://linkedlifedata.com/resource/pubmed/commentcorrection/19933801-9174209
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1098-6596
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
866-70
pubmed:dateRevised
2010-9-28
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Intrapulmonary pharmacokinetics of S-013420, a novel bicyclolide antibacterial, in healthy Japanese subjects.
pubmed:affiliation
Osaka Pharmacology Clinical Research Hospital, 41-1-29 Miyahara, Yodogawa-ku, Osaka-shi, Osaka 532-0003, Japan. GHA11244@nifty.com
pubmed:publicationType
Journal Article, Randomized Controlled Trial