Linked Life Data

10637778

Source:http://linkedlifedata.com/resource/pubmed/id/10637778

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-2-9
pubmed:abstractText
A 4-week repeated dose toxicity study of gadobenate dimeglumine formulation (E7155) was conducted in Sprague-Dawley rats to assess its non-clinical safety. E7155 was administered intravenously at doses of 0.3, 1.0 and 3.0 mmol/kg/day to male and female rats once a day during 4 weeks. The reversibility of toxicity was evaluated during a 4-week recovery period at 3.0 mmol/kg/day. At 0.3 mmol/kg/day and higher, vacuolation of the cortical epithelium was seen in the kidneys and an increase in the incidence of local damage at the injection sites. In the 1.0 and 3.0 mmol/kg/day male and female groups, scabbing/ulceration of the tail at the injection sites, macroscopic pale/thickened fundic mucosa in the stomachs, vacuolation of the urinary bladder, and mucosal mineralization with epithelial hyperplasia of the glandular stomach were found. In the 1.0 and 3.0 mmol/kg/day male group and 3.0 mmol/kg/day female group, increases of water consumption and urinary potassium excretion, increased kidney weight and enlargement of the kidneys were observed. In the 3.0 mmol/kg/day male and female group, hepatocyte necrosis with inflammatory cells in the liver and epithelial degranulation in the interlobular ducts of the salivary glands were found. In addition, in the 3.0 mmol/kg/day male group, increases in plasma sodium and decreases of urinary sodium and chloride excretion, and degenerative changes in the testes and epididymides were observed. After the 4-week recovery period, except for an increase in urinary potassium excretion, increased kidney weights and changes in the testes and epididymides, all of the above findings had complete or partial recovery. Vacuolation of renal tubular cells was common, expected, and known as an adaptive change of treatment with hypertonic solutions, and an increase in the incidence of local damage at the injection sites was due to irritation by repeated intravenous dosing with hypertonic solutions. Therefore, these changes were not toxic changes. In conclusion, the dose level of 0.3 mmol/kg/day should be regarded as the No Observed Adverse Effect Level (NOAEL) after repeated administration of E7155 in rats.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0388-1350
pubmed:author
pubmed:issnType
Print
pubmed:volume
24 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-39
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10637778-Animals, pubmed-meshheading:10637778-Blood Chemical Analysis, pubmed-meshheading:10637778-Body Weight, pubmed-meshheading:10637778-Contrast Media, pubmed-meshheading:10637778-Drinking, pubmed-meshheading:10637778-Eating, pubmed-meshheading:10637778-Eye, pubmed-meshheading:10637778-Female, pubmed-meshheading:10637778-Gadolinium, pubmed-meshheading:10637778-Hematologic Tests, pubmed-meshheading:10637778-Injections, Intravenous, pubmed-meshheading:10637778-Magnetic Resonance Imaging, pubmed-meshheading:10637778-Male, pubmed-meshheading:10637778-Meglumine, pubmed-meshheading:10637778-Organ Size, pubmed-meshheading:10637778-Organometallic Compounds, pubmed-meshheading:10637778-Rats, pubmed-meshheading:10637778-Rats, Sprague-Dawley, pubmed-meshheading:10637778-Time Factors, pubmed-meshheading:10637778-Urinalysis
pubmed:year
1999
pubmed:articleTitle
[General toxicity study of gadobenate dimeglumine formulation (E7155) (3)--4-week repeated dose intravenous toxicity study followed by 4-week recovery period in rats].
pubmed:affiliation
Department of Developmental Safety Assessment Research, Eisai Co., Ltd., Gifu, Japan.
pubmed:publicationType
Journal Article, English Abstract