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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1995-5-24
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pubmed:abstractText |
Rifabutin is a wide spectrum antibiotic particularly active on atypical and rifampicin-resistant mycobacteria. Rifabutin is more potent than rifampicin on Mycobacterium tuberculosis in vitro. Its mode of action is characterized by a high intracellular penetration in treated individuals. Clinical trials have proven the therapeutic value of rifabutin especially in AIDS patients with concomitant MAC. The preclinical safety evaluation of this compound included single and repeated dose toxicity studies of up to one year in rodents and non-rodents, reproduction and carcinogenicity studies and mutagenicity tests. During toxicological studies the most significant finding after repeated administration of rifabutin was the presence of multinucleated hepatocytes (MNH) in rats. This is a species specific finding which did not affect the life span of the hepatocytes. As shown in carcinogenicity studies, there was no tendency to further proliferative changes. Another specific histological feature among the species studied was the presence of a lipofuscin-like brown pigment, which was seen in many organs. This is a common finding with amphipilic compounds, such as rifabutin, which bind lipids and proteins, forming membrane-bound complexes. Even in carcinogenicity studies this change did not constitute a stimulus to cell proliferation and did not cause any secondary changes. In rodents, there was a mild hemolytic anemia at doses higher than 10 mg/kg/day. At doses ranging from 160-200 mg/kg/day rifabutin inhibited the functions of the male gonads in rats. This effect was reflected in a reduction of implantations observed in the fertility studies. Doses of 40 mg/kg/day did not induce any embryotoxic effects or changes in reproductive performance.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0940-2993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-9
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pubmed:dateRevised |
2006-10-30
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pubmed:meshHeading |
pubmed-meshheading:7719114-Administration, Oral,
pubmed-meshheading:7719114-Animals,
pubmed-meshheading:7719114-Carcinogens,
pubmed-meshheading:7719114-Female,
pubmed-meshheading:7719114-Injections, Intravenous,
pubmed-meshheading:7719114-Male,
pubmed-meshheading:7719114-Mutagens,
pubmed-meshheading:7719114-Reproduction,
pubmed-meshheading:7719114-Rifabutin
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pubmed:year |
1995
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pubmed:articleTitle |
Overview of toxicological data on rifabutin.
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pubmed:affiliation |
Pharmacia Farmitalia Carlo Erba, R & D/Toxicology Dpt., Nerviano (Milano), Italy.
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pubmed:publicationType |
Journal Article,
Review
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