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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
1996-12-16
|
| pubmed:abstractText |
Azithromycin reaches high concentrations in phagocytic and other host cells, suggesting that they may transport this agent to specific sites of infection. Models of localized infection (Haemophilus influenzae middle ear infection in gerbils, Streptococcus pyogenes implanted contaminated paper disc and Streptococcus pneumoniae pneumonia in mice) that induced severe inflammatory response after challenge were used to explore this hypothesis. Animals were given a single 100 or 50 mg/kg po dose of azithromycin at various times from 2 to 120 h following introduction of a pathogen or sterile medium. When azithromycin was given during a period of little or no inflammation, there was marginal difference between concentrations found in infected or non-infected sites (bulla, disc, lung). However, when the compound was given during a period of inflammation, considerably higher drug concentrations were found in infected sites than in non-infected sites at 5-24 h after dosing (0.38-0.44 mg/c compared with 0.07-0.14 mg/L of bulla wash; 1.01-1.75 micrograms compared with < or = 0.01-0.03 microgram at the disc site; 1.72-5.28 mg/kg compared with 0.7-1.53 mg/kg of lung). When the observation periods were extended to include 48, 56 or 96 h after dosing, the ratio of azithromycin infection site concentration: serum concentration steadily increased with time in all model systems (middle ear, implanted disc and pneumonia), reflecting the maintenance of concentrations at the sites of infection, while serum concentrations declined. Bioassay of cell pellets and supernatants, obtained from pooled bulla washes of gerbils treated with azithromycin during a period of inflammation, revealed that cellular components accounted for about 75% of the azithromycin detected. These data show that increased azithromycin concentrations occur at sites of localized infection. This correlates with the presence of inflammation and is associated with the cellular components of the inflammatory response. Therefore, phagocytes may be important vehicles for delivering azithromycin to and sustaining azithromycin concentrations at sites of infection.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0305-7453
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
37 Suppl C
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
9-19
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8818842-Animals,
pubmed-meshheading:8818842-Anti-Bacterial Agents,
pubmed-meshheading:8818842-Azithromycin,
pubmed-meshheading:8818842-Bacterial Infections,
pubmed-meshheading:8818842-Blister,
pubmed-meshheading:8818842-Female,
pubmed-meshheading:8818842-Gerbillinae,
pubmed-meshheading:8818842-Haemophilus Infections,
pubmed-meshheading:8818842-Haemophilus influenzae,
pubmed-meshheading:8818842-Lung,
pubmed-meshheading:8818842-Male,
pubmed-meshheading:8818842-Mice,
pubmed-meshheading:8818842-Otitis Media,
pubmed-meshheading:8818842-Phagocytes,
pubmed-meshheading:8818842-Pneumococcal Infections,
pubmed-meshheading:8818842-Streptococcal Infections,
pubmed-meshheading:8818842-Streptococcus pneumoniae,
pubmed-meshheading:8818842-Streptococcus pyogenes
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Correlation of increased azithromycin concentrations with phagocyte infiltration into sites of localized infection.
|
| pubmed:affiliation |
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
|
| pubmed:publicationType |
Journal Article
|