Linked Life Data

9657047

Source:http://linkedlifedata.com/resource/pubmed/id/9657047

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-9-4
pubmed:abstractText
Tacrolimus, an immunosuppressive agent, is metabolized mainly in the liver and has shown large intra- and interindividual pharmacokinetic variability. We investigated the effect of liver dysfunctions on the pharmacokinetics of tacrolimus in rats with experimental liver diseases. Experimental hepatic failure was induced by CCl4-treatment or bile duct ligation. Tacrolimus (1 or 0.3 mg/kg) was administered intravenously or intraportally to the rats (n = 5-6 per group), and blood samples were collected over a 240-min period. The tacrolimus concentrations in the blood were then measured by a high-performance liquid chromatography-enzyme immunoassay. In the normal rats, the hepatic extraction ratio of tacrolimus (EH) was dose-independent, ranging from 0.556-0.598 at 0.3 and 1.0 mg/kg doses. The EH were dose-dependent in the CCl4-treated rats and in the bile duct-ligated rats: the EH at 1.0 mg/kg dose were 0.158-0.170 and those at 0.3 mg/kg dose were 0.329-0.394. The intermediate EH of tacrolimus suggested that the clearance of tacrolimus depends not only on hepatic intrinsic clearance but also on hepatic blood flow. The present pharmacokinetic study also suggested that the decrease of EH and the dose-dependence of EH contribute to the elevation of blood tacrolimus concentrations and to the large variability in the pharmacokinetics of tacrolimus after oral administration in hepatic dysfunctions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0918-6158
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
610-4
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Hepatic extraction of tacrolimus in rats with experimental liver diseases.
pubmed:affiliation
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't