Linked Life Data

18443034

Source:http://linkedlifedata.com/resource/pubmed/id/18443034

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-7-22
pubmed:abstractText
Expression of the organic anion transporting polypeptide 1B1 (OATP1B1) is regulated by transcription factor hepatic nuclear factor (HNF) 1alpha. The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA), an inhibitor of transcription factor HNF1alpha, on rosuvastatin and bilirubin kinetics in human healthy volunteers. Both substances are substrates of OATP1B1. Twelve subjects with OATP1B1(*)1b/(*)1b genotype predicting high transport activity were recruited for this randomized, crossover study. Each subject received a single p.o. dose of 20 mg of rosuvastatin after 14 days of p.o. intake of either 500 mg of UDCA or placebo. Plasma concentrations of rosuvastatin were determined on days 15 to 18 of each study period. Subjects were randomly assigned to UDCA or placebo group. Intake of UDCA led to a significant increase in rosuvastatin area under the curve (AUC)(0-72) from 128.5 ng/ml.h to 182.1 ng/ml.h(P = 0.008) compared with the control group. The oral clearance decreased from 155.2 l/h with placebo to 109.8 l/h with UDCA. In addition, the mean values of total bilirubin, conjugated bilirubin, and unconjugated bilirubin significantly increased to 139 +/- 39% (P = 0.003), 127 +/- 29% (P = 0.005), and 151 +/- 52% (P = 0.004), respectively, after UDCA treatment. These results in healthy volunteers confirm the findings from in vitro studies that UDCA inhibits OATP1B1 activity by inhibition of the transcription factor HNF1alpha. They highlight a novel mechanism of OATP1B1-based interaction that is mediated by transcription factor HNF1alpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1453-6
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Hepatic nuclear factor 1alpha inhibitor ursodeoxycholic acid influences pharmacokinetics of the organic anion transporting polypeptide 1B1 substrate rosuvastatin and bilirubin.
pubmed:affiliation
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, China.
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't