Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-5-24
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)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0940-2993
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-9
pubmed:dateRevised
2006-10-30
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Overview of toxicological data on rifabutin.
pubmed:affiliation
Pharmacia Farmitalia Carlo Erba, R & D/Toxicology Dpt., Nerviano (Milano), Italy.
pubmed:publicationType
Journal Article, Review