Linked Life Data

15919446

Source:http://linkedlifedata.com/resource/pubmed/id/15919446

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-5-27
pubmed:abstractText
The role of intestinal P-glycoprotein (encoded by the MDR1/ABCB1 gene) and/or metabolic enzyme CYP3A4 for tacrolimus therapy was examined in recipients of living-donor liver transplantation (LDLT), under the hypothesis that these proteins are factors for pharmacokinetic variability. The intestinal mRNA expression level of MDR1 and CYP3A4 was evaluated by real-time polymerase chain reaction (PCR), using the upper jejunum from a part of the Roux-en-Y limb for biliary reconstruction at LDLT. For 7 days postoperatively, good inverse correlation was found between the tacrolimus concentration/dose (C/D) ratio and the intestinal mRNA level of MDR1 (r = -0.776), but not of CYP3A4 (r = -0.096), in the 46 cases. After classifying the patients according to median of the intestinal MDR1 mRNA expression, the oral dose of tacrolimus in the high-MDR1 group was approximately twofold higher than in the low-MDR1 group (P < .001), whereas its trough level was similar between the two groups. In addition, the correlation between the intestinal MDR1 mRNA level and the tacrolimus C/D ratio was confirmed with a larger population (r = -0.645, n = 104). Using the regression line between the intestinal MDR1 mRNA level and tacrolimus C/D ratio, we could prospectively predict the individual C/D ratio of tacrolimus immediately after LDLT. Known genetic variations of the MDR1 gene had no effect on intestinal MDR1 mRNA level and tacrolimus C/D ratio in LDLT patients. This suggests that the intestinal mRNA level of MDR1 is a useful molecular marker for determination of the personalized oral dose of tacrolimus in recipients of LDLT immediately after surgery.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0041-1345
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1728-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Initial dosage adjustment for oral administration of tacrolimus using the intestinal MDR1 level in living-donor liver transplant recipients.
pubmed:affiliation
Department of Pharmacy, Kyoto University Hospital, Kyoto University, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't