Linked Life Data

19776292

Source:http://linkedlifedata.com/resource/pubmed/id/19776292

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-10-21
pubmed:abstractText
The aims of this study were to develop a population pharmacokinetic (PPK) model for pravastatin pharmacokinetics with regard to enterohepatic circulation (EHC) and to evaluate effects of polymorphisms in SLCO1B1 and ABCC2 on the pharmacokinetic (PK) profile of pravastatin quantitatively. A total of 636 blood samples from 57 healthy male volunteers were used. The PPK analysis was carried out using nonlinear mixed effect modeling (NONMEM) and validated by a bootstrap analysis. The PK profile of pravastatin was best described by a model of EHC with Erlang's distribution. A covariate analysis revealed that SLCO1B1(*)15 significantly influenced relative bioavailability (F(rel)); F(rel) was increased 1.50- and 1.95-fold in participants heterozygous and homozygous, respectively, for the (*)15 allele in comparison with participants without the allele. No ABCC2 polymorphism was identified as a potential covariate for pravastatin. The bootstrap analysis indicated that the PK profile of pravastatin was adequately described by the proposed PPK model. SLCO1B1(*)15 has a significant effect on F(rel), indicating that OATP1B1 is one of the determinants of systemic exposure to pravastatin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1552-4604
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1309-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Quantitative population pharmacokinetic analysis of pravastatin using an enterohepatic circulation model combined with pharmacogenomic Information on SLCO1B1 and ABCC2 polymorphisms.
pubmed:affiliation
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Validation Studies