Linked Life Data

2607557

Source:http://linkedlifedata.com/resource/pubmed/id/2607557

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1990-2-21
pubmed:abstractText
A subacute oral toxicity study of propiverine hydrochloride (P-4), a new anti-pollakiuria agent, was carried out at dose-levels of 0, 1, 3, 9, and 27 mg/kg/day using male and female beagle dogs. They were treated for 13 weeks, followed by 5 weeks recovery period. The results obtained from the present study were as follows. 1. In the observation of general symptoms, mydriasis was observed in females receiving 3 mg/kg/day or more and in males receiving 9 mg/kg/day or more, every day, intermittently or sporadically. The incidence of mydriasis varied greatly in individuals. However, this sign disappeared within administration period. 2. Body weight gain was slightly suppressed in males and females receiving 27 mg/kg/day. 3. There were no significant changes in food consumption, water consumption, hematology, urinalysis and fecal occult blood, and no remarkable changes in ophthalmology, electrocardiogram. 4. Serum biochemical findings showed a decrease in Total cholesterol (T. cho), Free cholesterol (F. cho), Triglyceride (TG), Phospholipid (PL), Total protein (TP), Albumin (ALB), alpha 1-Globulin (alpha 1-GLO) and Calcium (Ca), and an increase in Alkaline phosphatase (Al P), gamma-Glutamyltranspeptidase (gamma-GTP) activities and Choresterol ester ratio (EST/T) in males and females receiving 27 mg/kg/day. Further, a decrease in lipoprotein-T. cho, -TG and -PL were noted, on the other hand, lipoprotein-T. cho, -TG and -PL in the liver tissue increased. Similar slight changes were observed in males and females receiving 9 mg/kg/day. 5. Pathological examination revealed an enlargement of hepatocytes in a few animals receiving 3 mg/kg/day. In males and females receiving 9 mg/kg/day or more, yellowish liver, a increase in liver weights, an enlargement of hepatocytes with fatty degeneration and the appearance of eosinophilic inclusions in the hepatocytes were observed. Furthermore, some males and females receiving 27 mg/kg/day showed a slight cellular infiltration in glisson's sheaths, proliferation of the bile ducts and deposition of lipid droplets. Histochemical examination of liver tissue showed an increase in Al P and gamma-GTP activities in addition. Electronmicroscopically, the proliferation of smooth endoplasmic reticulum, increases in myelin-like inclusions and small lipid droplets in the hepatocytes were noted and these changes suggested the induction of drug-metabolizing enzyme in the liver. 6. After 5 weeks recovery period, above-mentioned changes were disappeared and it was suggested that these were reversible ones. 7. From the above results, the non-effective dose and the toxic one were estimated to be 1 mg/kg/day and 9 mg/kg/day for males and females, respectively.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0388-1350
pubmed:author
pubmed:issnType
Print
pubmed:volume
14 Suppl 2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-109
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
[Thirteen-week oral toxicity study of propiverine hydrochloride in dogs].
pubmed:affiliation
Drug Safety Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
pubmed:publicationType
Journal Article, English Abstract