| pubmed-article:9657047 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9657047 | lifeskim:mentions | umls-concept:C0023895 | lld:lifeskim |
| pubmed-article:9657047 | lifeskim:mentions | umls-concept:C0034693 | lld:lifeskim |
| pubmed-article:9657047 | lifeskim:mentions | umls-concept:C0205054 | lld:lifeskim |
| pubmed-article:9657047 | lifeskim:mentions | umls-concept:C0085149 | lld:lifeskim |
| pubmed-article:9657047 | lifeskim:mentions | umls-concept:C0185115 | lld:lifeskim |
| pubmed-article:9657047 | lifeskim:mentions | umls-concept:C1517004 | lld:lifeskim |
| pubmed-article:9657047 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:9657047 | pubmed:dateCreated | 1998-9-4 | lld:pubmed |
| pubmed-article:9657047 | 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. | lld:pubmed |
| pubmed-article:9657047 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9657047 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9657047 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9657047 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9657047 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9657047 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9657047 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:9657047 | pubmed:issn | 0918-6158 | lld:pubmed |
| pubmed-article:9657047 | pubmed:author | pubmed-author:ShimizuTT | lld:pubmed |
| pubmed-article:9657047 | pubmed:author | pubmed-author:HashimotoYY | lld:pubmed |
| pubmed-article:9657047 | pubmed:author | pubmed-author:SasaHH | lld:pubmed |
| pubmed-article:9657047 | pubmed:author | pubmed-author:InuiKK | lld:pubmed |
| pubmed-article:9657047 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9657047 | pubmed:volume | 21 | lld:pubmed |
| pubmed-article:9657047 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9657047 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9657047 | pubmed:pagination | 610-4 | lld:pubmed |
| pubmed-article:9657047 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:meshHeading | pubmed-meshheading:9657047-... | lld:pubmed |
| pubmed-article:9657047 | pubmed:year | 1998 | lld:pubmed |
| pubmed-article:9657047 | pubmed:articleTitle | Hepatic extraction of tacrolimus in rats with experimental liver diseases. | lld:pubmed |
| pubmed-article:9657047 | pubmed:affiliation | Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan. | lld:pubmed |
| pubmed-article:9657047 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:9657047 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
