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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1997-10-1
|
| pubmed:abstractText |
KRM-1648 is a new benzoxazinorifamycin with activity in vitro and in vivo against organisms of the Mycobacterium avium complex. We investigated the ability of 14C-KRM-1648 to concentrate within human monocyte-derived macrophages in vitro. KRM-1648 is rapidly taken up by uninfected macrophages, with 90% of the initial concentration added to the monolayer found within macrophages by 1 h and approximately 80% at 2 h. Comparable results were obtained in assays using macrophages that have been infected with an AIDS-related strain of M. avium for 24 h. In contrast, macrophages infected with M. avium for 3 days, showed an impaired ability to concentrate KRM-1648, primarily because of a significant efflux of the antibiotic (intracellular concentration of 86% of the available drug was present within macrophages at 1 h vs. 47% at 2 h). Daily administrations of KRM-1648 to a macrophage monolayer for 3 consecutive days resulted in significant accumulation of the drug within phagocytic cells. Although the efflux was greater in M. avium-infected macrophages than in uninfected cells, consecutive administration of KRM-1648 led to a total intracellular accumulation of drug that exceeded the initial level and appeared to continue to accumulate. The ability of KRM-1648 to rapidly accumulate in human macrophages, including M. avium-infected cells, may explain, in part, the improved therapeutic effectiveness in animal models against M. avium and M. tuberculosis.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
1076-6294
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
3
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
277-82
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9270999-Adult,
pubmed-meshheading:9270999-Antibiotics, Antitubercular,
pubmed-meshheading:9270999-Biological Transport,
pubmed-meshheading:9270999-Carbon Radioisotopes,
pubmed-meshheading:9270999-Female,
pubmed-meshheading:9270999-Humans,
pubmed-meshheading:9270999-Macrophages,
pubmed-meshheading:9270999-Male,
pubmed-meshheading:9270999-Middle Aged,
pubmed-meshheading:9270999-Monocytes,
pubmed-meshheading:9270999-Mycobacterium avium-intracellulare Infection,
pubmed-meshheading:9270999-Rifamycins
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Effect of Mycobacterium avium infection on the influx, accumulation, and efflux of KRM-1648 by human macrophages.
|
| pubmed:affiliation |
Kuzell Institute for Arthritis & Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115, USA.
|
| pubmed:publicationType |
Journal Article
|