Linked Life Data

17301738

Source:http://linkedlifedata.com/resource/pubmed/id/17301738

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-21
pubmed:abstractText
The aim of this study was to characterize the relationship between warfarin concentrations and international normalized ratio (INR) response and to identify predictors important for dose individualization. S- and R-warfarin concentrations, INR, and CYP2C9 and VKORC1 genotypes from 150 patients were used to develop a population pharmacokinetic/pharmacodynamic model in NONMEM. The anticoagulant response was best described by an inhibitory E(MAX) model, with S-warfarin concentration as the only exposure predictor for response. Delay between exposure and response was accounted for by a transit compartment model with two parallel transit compartment chains. CYP2C9 genotype and age were identified as predictors for S-warfarin clearance, and VKORC1 genotype as a predictor for warfarin sensitivity. Predicted INR curves indicate important steady-state differences between patients with different sets of covariates; differences that cannot be foreseen from early INR assessments alone. It is important to account for CYP2C9 and VKORC1 genotypes and age to improve a priori and a posteriori individualization of warfarin therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
529-38
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
A PK-PD model for predicting the impact of age, CYP2C9, and VKORC1 genotype on individualization of warfarin therapy.
pubmed:affiliation
Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden. anna-karin.hamberg@roche.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't